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Review

Role of the tumor microenvironment in tumor progression and the clinical applications (Review)

  • Authors:
    • Yao Yuan
    • Yu-Chen Jiang
    • Chong-Kui Sun
    • Qian-Ming Chen
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China
  • Pages: 2499-2515
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    Published online on: March 7, 2016
       https://doi.org/10.3892/or.2016.4660
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Abstract

Oncogene activation and tumor-suppressor gene inactivation are considered as the main causes driving the transformation of normal somatic cells into malignant tumor cells. Cancer cells are the driving force of tumor development and progression. Yet, cancer cells are unable to accomplish this alone. The tumor microenvironment is also considered to play an active role rather than simply acting as a by-stander in tumor progression. Through different pathways, tumor cells efficiently recruit stromal cells, which in turn, provide tumor cell growth signals, intermediate metabolites, and provide a suitable environment for tumor progression as well as metastasis. Through reciprocal communication, cancer cells and the microenvironment act in collusion leading to high proliferation and metastatic capability. Understanding the role of the tumor microenvironment in tumor progression provides us with novel approaches through which to target the tumor microenvironment for efficient anticancer treatment. In this review, we summarize the mechanisms involved in the recruitment of stromal cells by tumor cells to the primary tumor site and highlight the role of the tumor microenvironment in the regulation of tumor progression. We further discuss the potential approaches for cancer therapy.
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1 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Hanahan D and Coussens LM: Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell. 21:309–322. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Cirri P and Chiarugi P: Cancer associated fibroblasts: The dark side of the coin. Am J Cancer Res. 1:482–497. 2011.PubMed/NCBI

5 

Gabrilovich DI, Ostrand-Rosenberg S and Bronte V: Coordinated regulation of myeloid cells by Tumours. Nat Rev Immunol. 12:253–268. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Cheng L, Huang Z, Zhou W, Wu Q, Donnola S, Liu JK, Fang X, Sloan AE, Mao Y, Lathia JD, et al: Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 153:139–152. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Cornil I, Theodorescu D, Man S, Herlyn M, Jambrosic J and Kerbel RS: Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression. Proc Natl Acad Sci USA. 88:6028–6032. 1991. View Article : Google Scholar : PubMed/NCBI

8 

Räsänen K and Vaheri A: Activation of fibroblasts in cancer stroma. Exp Cell Res. 316:2713–2722. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Lu C, Vickers MF and Kerbel RS: Interleukin 6: A fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. Proc Natl Acad Sci USA. 89:9215–9219. 1992. View Article : Google Scholar : PubMed/NCBI

10 

Leonardi GC, Candido S, Cervello M, Nicolosi D, Raiti F, Travali S, Spandidos DA and Libra M: The tumor microenvironment in hepatocellular carcinoma (review). Int J Oncol. 40:1733–1747. 2012.PubMed/NCBI

11 

Rønnov-Jessen L and Petersen OW: Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. Lab Invest. 68:696–707. 1993.PubMed/NCBI

12 

Postlethwaite AE, Keski-Oja J, Moses HL and Kang AH: Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 165:251–256. 1987. View Article : Google Scholar : PubMed/NCBI

13 

Mayo LD, Dixon JE, Durden DL, Tonks NK and Donner DB: PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Biol Chem. 277:5484–5489. 2002. View Article : Google Scholar

14 

Erez N, Truitt M, Olson P, Arron ST and Hanahan D: Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell. 17:135–147. 2010. View Article : Google Scholar : PubMed/NCBI

15 

De Wever O, Demetter P, Mareel M and Bracke M: Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer. 123:2229–2238. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Schmitt-Gräff A, Desmoulière A and Gabbiani G: Heterogeneity of myofibroblast phenotypic features: An example of fibroblastic cell plasticity. Virchows Arch. 425:3–24. 1994. View Article : Google Scholar : PubMed/NCBI

17 

Tlsty TD and Hein PW: Know thy neighbor: Stromal cells can contribute oncogenic signals. Curr Opin Genet Dev. 11:54–59. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Skalli O, Pelte MF, Peclet MC, Gabbiani G, Gugliotta P, Bussolati G, Ravazzola M and Orci L: Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes. J Histochem Cytochem. 37:315–321. 1989. View Article : Google Scholar : PubMed/NCBI

19 

De Wever O and Mareel M: Role of tissue stroma in cancer cell invasion. J Pathol. 200:429–447. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Rattigan Y, Hsu JM, Mishra PJ, Glod J and Banerjee D: Interleukin 6 mediated recruitment of mesenchymal stem cells to the hypoxic tumor milieu. Exp Cell Res. 316:3417–3424. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R and Weinberg RA: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449:557–563. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, et al: Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 13:952–961. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Zeisberg EM, Potenta S, Xie L, Zeisberg M and Kalluri R: Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 67:10123–10128. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Petersen OW, Lind Nielsen H, Gudjonsson T, Villadsen R, Rønnov-Jessen L and Bissell MJ: The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion. Breast Cancer Res. 3:213–217. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Petersen OW, Nielsen HL, Gudjonsson T, Villadsen R, Rank F, Niebuhr E, Bissell MJ and Rønnov-Jessen L: Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma. Am J Pathol. 162:391–402. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP and Eng C: Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet. 32:355–357. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Orimo A and Weinberg RA: Stromal fibroblasts in cancer: A novel tumor-promoting cell type. Cell Cycle. 5:1597–1601. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Bronisz A, Godlewski J, Wallace JA, Merchant AS, Nowicki MO, Mathsyaraja H, Srinivasan R, Trimboli AJ, Martin CK, Li F, et al: Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol. 14:159–167. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Sun X, Mao Y, Wang J, Zu L, Hao M, Cheng G, Qu Q, Cui D, Keller ET, Chen X, et al: IL-6 secreted by cancer-associated fibroblasts induces tamoxifen resistance in luminal breast cancer. Oncogene. Jun 9–2014.Epub ahead of print. View Article : Google Scholar

31 

Sica A: Role of tumour-associated macrophages in cancer-related inflammation. Exp Oncol. 32:153–158. 2010.

32 

Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P and Mantovani A: Macrophage polarization in tumour progression. Semin Cancer Biol. 18:349–355. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Lin EY, Nguyen AV, Russell RG and Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 193:727–740. 2001. View Article : Google Scholar : PubMed/NCBI

34 

Nesbit M, Schaider H, Miller TH and Herlyn M: Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. J Immunol. 166:6483–6490. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, Acevedo LM, Manglicmot JR, Song X, Wrasidlo W, et al: Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 19:715–727. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Balkwill F: Cancer and the chemokine network. Nat Rev Cancer. 4:540–550. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR and Kaiser EA: CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 475:222–225. 2011. View Article : Google Scholar : PubMed/NCBI

38 

Mizutani K, Sud S, McGregor NA, Martinovski G, Rice BT, Craig MJ, Varsos ZS, Roca H and Pienta KJ: The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment. Neoplasia. 11:1235–1242. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, et al: A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell. 150:165–178. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Shields JD, Kourtis IC, Tomei AA, Roberts JM and Swartz MA: Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science. 328:749–752. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Cremer I, Fridman WH and Sautès-Fridman C: Tumor microenvironment in NSCLC suppresses NK cells function. Oncoimmunology. 1:244–246. 2012. View Article : Google Scholar : PubMed/NCBI

42 

Zhao X, Rong L, Zhao X, Li X, Liu X, Deng J, Wu H, Xu X, Erben U, Wu P, et al: TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest. 122:4094–4104. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ and Vonderheide RH: Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell. 21:822–835. 2012. View Article : Google Scholar : PubMed/NCBI

44 

Würth R, Bajetto A, Harrison JK, Barbieri F and Florio T: CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor micro-environment. Front Cell Neurosci. 8:1442014.

45 

Bergers G and Benjamin LE: Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 3:401–410. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Bertolini F, Shaked Y, Mancuso P and Kerbel RS: The multifaceted circulating endothelial cell in cancer: Towards marker and target identification. Nat Rev Cancer. 6:835–845. 2006. View Article : Google Scholar : PubMed/NCBI

47 

Volm M, Koomägi R and Mattern J: Prognostic value of vascular endothelial growth factor and its receptor FLT-1 in squamous cell lung cancer. Int J Cancer. 74:64–68. 1997. View Article : Google Scholar : PubMed/NCBI

48 

Yoshiji H, Gomez DE, Shibuya M and Thorgeirsson UP: Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 56:2013–2016. 1996.PubMed/NCBI

49 

Olson TA, Mohanraj D, Carson LF and Ramakrishnan S: Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res. 54:276–280. 1994.PubMed/NCBI

50 

Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF and Senger DR: Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 143:1255–1262. 1993.PubMed/NCBI

51 

Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M and Isner JM: VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 18:3964–3972. 1999. View Article : Google Scholar : PubMed/NCBI

52 

Png KJ, Halberg N, Yoshida M and Tavazoie SF: A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 481:190–194. 2011. View Article : Google Scholar : PubMed/NCBI

53 

Zeng Z, Li YC, Jiao ZH, Yao J and Xue Y: The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell angiogenesis. Int J Mol Sci. 15:10185–10198. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Karar J and Maity A: PI3K/AKT/mTOR pathway in angiogenesis. Front Mol Neurosci. 4:512011. View Article : Google Scholar : PubMed/NCBI

55 

Wang Z, Martin D, Molinolo AA, Patel V, Iglesias-Bartolome R, Degese MS, Vitale-Cross L, Chen Q and Gutkind JS: mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations. J Natl Cancer Inst. 106:dju2152014. View Article : Google Scholar : PubMed/NCBI

56 

Patel V, Marsh CA, Dorsam RT, Mikelis CM, Masedunskas A, Amornphimoltham P, Nathan CA, Singh B, Weigert R, Molinolo AA, et al: Decreased lymphangiogenesis and lymph node metastasis by mTOR inhibition in head and neck cancer. Cancer Res. 71:7103–7112. 2011. View Article : Google Scholar : PubMed/NCBI

57 

Oft M, Heider KH and Beug H: TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol. 8:1243–1252. 1998. View Article : Google Scholar : PubMed/NCBI

58 

Biswas S, Guix M, Rinehart C, Dugger TC, Chytil A, Moses HL, Freeman ML and Arteaga CL: Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J Clin Invest. 117:1305–1313. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR and Massagué J: TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell. 133:66–77. 2008. View Article : Google Scholar : PubMed/NCBI

60 

Siegel PM, Shu W, Cardiff RD, Muller WJ and Massagué J: Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA. 100:8430–8435. 2003. View Article : Google Scholar : PubMed/NCBI

61 

Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massagué J, Mundy GR and Guise TA: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 103:197–206. 1999. View Article : Google Scholar : PubMed/NCBI

62 

Kang Y, HE W, Tulley S, Gupta GP, Serganova I, Chen CR, Manova-Todorova K, Blasberg R, Gerald WL and Massagué J: Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci USA. 102:13909–13914. 2005. View Article : Google Scholar : PubMed/NCBI

63 

Labelle M, Begum S and Hynes RO: Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 20:576–590. 2011. View Article : Google Scholar : PubMed/NCBI

64 

Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K and Shimizu S: Molecular cloning and expression of human hepatocyte growth factor. Nature. 342:440–443. 1989. View Article : Google Scholar : PubMed/NCBI

65 

Birchmeier C, Birchmeier W, Gherardi E and Vande Woude GF: Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 4:915–925. 2003. View Article : Google Scholar : PubMed/NCBI

66 

Matsumoto K and Nakamura T: Hepatocyte growth factor and the met system as a mediator of tumor-stromal interactions. Int J Cancer. 119:477–483. 2006. View Article : Google Scholar : PubMed/NCBI

67 

Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, et al: Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature. 487:505–509. 2012. View Article : Google Scholar : PubMed/NCBI

68 

Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, et al: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 487:500–504. 2012. View Article : Google Scholar : PubMed/NCBI

69 

Zhou P, Li H, Wheeler S, Grandis JR, Stabile LA and Egloff AM: Generation of head and neck cancer patient-derived xenografts with in vivo acquired cetuximab resistance. Clin Cancer Res. 21(Suppl 4): B392015. View Article : Google Scholar

70 

Rossi D and Zlotnik A: The biology of chemokines and their receptors. Annu Rev Immunol. 18:217–242. 2000. View Article : Google Scholar : PubMed/NCBI

71 

Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ and Power CA: International union of pharmacology. XXII Nomenclature for chemokine receptors. Pharmacol Rev. 52:145–176. 2000.PubMed/NCBI

72 

Zlotnik A and Yoshie O: Chemokines: A new classification system and their role in immunity. Immunity. 12:121–127. 2000. View Article : Google Scholar : PubMed/NCBI

73 

Dhawan P and Richmond A: Role of CXCL1 in tumorigenesis of melanoma. J Leukoc Biol. 72:9–18. 2002.PubMed/NCBI

74 

Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q, Richmond A, Strieter R, Dey SK and DuBois RN: CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med. 203:941–951. 2006. View Article : Google Scholar : PubMed/NCBI

75 

Karunagaran D, Tzahar E, Beerli RR, Chen X, Graus-Porta D, Ratzkin BJ, Seger R, Hynes NE and Yarden Y: ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer. EMBO J. 15:254–264. 1996.PubMed/NCBI

76 

Conti I and Rollins BJ: CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol. 14:149–154. 2004. View Article : Google Scholar : PubMed/NCBI

77 

Craig MJ and Loberg RD: CCL2 (monocyte chemoattractant protein-1) in cancer bone metastases. Cancer Metastasis Rev. 25:611–619. 2006. View Article : Google Scholar : PubMed/NCBI

78 

Popivanova BK, Kostadinova FI, Furuichi K, Shamekh MM, Kondo T, Wada T, Egashira K and Mukaida N: Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice. Cancer Res. 69:7884–7892. 2009. View Article : Google Scholar : PubMed/NCBI

79 

Rottiers V and Näär AM: MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 13:239–250. 2012. View Article : Google Scholar : PubMed/NCBI

80 

Krützfeldt J and Stoffel M: MicroRNAs: A new class of regulatory genes affecting metabolism. Cell Metab. 4:9–12. 2006. View Article : Google Scholar : PubMed/NCBI

81 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

82 

Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y and Ochiya T: Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 285:17442–17452. 2010. View Article : Google Scholar : PubMed/NCBI

83 

Zhang J, Zhao H, Gao Y and Zhang W: Secretory miRNAs as novel cancer biomarkers. Biochim Biophys Acta. 1826:32–43. 2012.PubMed/NCBI

84 

Xu D and Tahara H: The role of exosomes and microRNAs in senescence and aging. Adv Drug Deliv Rev. 65:368–375. 2013. View Article : Google Scholar

85 

Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F and Ochiya T: Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. 287:1397–1405. 2012. View Article : Google Scholar :

86 

Yang M, Chen J, Su F, Yu B, Su F, Lin L, Liu Y, Huang JD and Song E: Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 10:1172011. View Article : Google Scholar : PubMed/NCBI

87 

Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, Lovat F, Fadda P, Mao C, Nuovo GJ, et al: MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 109:E2110–E2116. 2012. View Article : Google Scholar : PubMed/NCBI

88 

Roth C, Rack B, Müller V, Janni W, Pantel K and Schwarzenbach H: Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 12:R902010. View Article : Google Scholar : PubMed/NCBI

89 

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, et al: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar : PubMed/NCBI

90 

Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar : PubMed/NCBI

91 

Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI

92 

Lunt SY and Vander Heiden MG: Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol. 27:441–464. 2011. View Article : Google Scholar : PubMed/NCBI

93 

Riemann A, Schneider B, Ihling A, Nowak M, Sauvant C, Thews O and Gekle M: Acidic environment leads to ROS-induced MAPK signaling in cancer cells. PLoS One. 6:e224452011. View Article : Google Scholar : PubMed/NCBI

94 

Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al: Inhibitory effect of tumor cell-derived lactic acid on human t cells. Blood. 109:3812–3819. 2007. View Article : Google Scholar : PubMed/NCBI

95 

Walenta S and Mueller-Klieser WF: Lactate: Mirror and motor of tumor malignancy. Semin Radiat Oncol. 14:267–274. 2004. View Article : Google Scholar : PubMed/NCBI

96 

Rattigan YI, Patel BB, Ackerstaff E, Sukenick G, Koutcher JA, Glod JW and Banerjee D: Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment. Exp Cell Res. 318:326–335. 2012. View Article : Google Scholar :

97 

Végran F, Boidot R, Michiels C, Sonveaux P and Feron O: Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 71:2550–2560. 2011. View Article : Google Scholar

98 

Semenza GL: Tumor metabolism: Cancer cells give and take lactate. J Clin Invest. 118:3835–3837. 2008.PubMed/NCBI

99 

Feron O: Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells. Radiother Oncol. 92:329–333. 2009. View Article : Google Scholar : PubMed/NCBI

100 

Sonveaux P, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, et al: Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 118:3930–3942. 2008.PubMed/NCBI

101 

Koukourakis MI, Giatromanolaki A, Harris AL and Sivridis E: Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: A metabolic survival role for tumor-associated stroma. Cancer Res. 66:632–637. 2006. View Article : Google Scholar : PubMed/NCBI

102 

Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, et al: Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 17:1498–1503. 2011. View Article : Google Scholar : PubMed/NCBI

103 

Marie SK and Shinjo SM: Metabolism and brain cancer. Clinics (Sao Paulo). 66(Suppl 1): 33–43. 2011. View Article : Google Scholar

104 

Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M, et al: Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 69:4918–4925. 2009. View Article : Google Scholar : PubMed/NCBI

105 

Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP and Martinez-Outschoorn UE: Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: Implications for preventing chemotherapy resistance. Cancer Biol Ther. 12:1085–1097. 2011. View Article : Google Scholar

106 

Filipp FV, Ratnikov B, De Ingeniis J, Smith JW, Osterman AL and Scott DA: Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma. Pigment Cell Melanoma Res. 25:732–739. 2012. View Article : Google Scholar : PubMed/NCBI

107 

Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB and Mootha VK: Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science. 336:1040–1044. 2012. View Article : Google Scholar : PubMed/NCBI

108 

Okamoto K, Toyokuni S, Kim WJ, Ogawa O, Kakehi Y, Arao S, Hiai H and Yoshida O: Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer. Int J Cancer. 65:437–441. 1996. View Article : Google Scholar : PubMed/NCBI

109 

Gackowski D, Banaszkiewicz Z, Rozalski R, Jawien A and Olinski R: Persistent oxidative stress in colorectal carcinoma patients. Int J Cancer. 101:395–397. 2002. View Article : Google Scholar : PubMed/NCBI

110 

Toyokuni S, Okamoto K, Yodoi J and Hiai H: Persistent oxidative stress in cancer. FEBS Lett. 358:1–3. 1995. View Article : Google Scholar : PubMed/NCBI

111 

Zhou Y, Hileman EO, Plunkett W, Keating MJ and Huang P: Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. Blood. 101:4098–4104. 2003. View Article : Google Scholar : PubMed/NCBI

112 

Szatrowski TP and Nathan CF: Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51:794–798. 1991.PubMed/NCBI

113 

Grivennikov SI, Greten FR and Karin M: Immunity, inflammation, and cancer. Cell. 140:883–899. 2010. View Article : Google Scholar : PubMed/NCBI

114 

Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y and Hayashi J: ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science. 320:661–664. 2008. View Article : Google Scholar : PubMed/NCBI

115 

Trachootham D, Alexandre J and Huang P: Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov. 8:579–591. 2009. View Article : Google Scholar : PubMed/NCBI

116 

Martinez-Outschoorn UE, Lin Z, Trimmer C, Flomenberg N, Wang C, Pavlides S, Pestell RG, Howell A, Sotgia F and Lisanti MP: Cancer cells metabolically 'fertilize' the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: Implications for Pet imaging of human tumors. Cell Cycle. 10:2504–2520. 2011. View Article : Google Scholar : PubMed/NCBI

117 

Mathew R, Karantza-Wadsworth V and White E: Role of autophagy in cancer. Nat Rev Cancer. 7:961–967. 2007. View Article : Google Scholar : PubMed/NCBI

118 

Baehrecke EH: Autophagy: Dual roles in life and death? Nat Rev Mol Cell Biol. 6:505–510. 2005. View Article : Google Scholar : PubMed/NCBI

119 

Eisenberg-Lerner A and Kimchi A: The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis. 14:376–391. 2009. View Article : Google Scholar : PubMed/NCBI

120 

Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, et al: The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle. 9:3485–3505. 2010. View Article : Google Scholar : PubMed/NCBI

121 

Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, et al: Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle. 9:3256–3276. 2010. View Article : Google Scholar : PubMed/NCBI

122 

Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al: Ketones and lactate 'fuel' tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 9:3506–3514. 2010. View Article : Google Scholar : PubMed/NCBI

123 

Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, et al: Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment. Cell Cycle. 9:3515–3533. 2010. View Article : Google Scholar : PubMed/NCBI

124 

Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, Tanowitz HB, Casimiro MC, Wang C, Pestell RG, et al: HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis. Cell Cycle. 9:3534–3551. 2010. View Article : Google Scholar : PubMed/NCBI

125 

Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, Tsirigos A, Migneco G, Witkiewicz A, Balliet R, et al: The autophagic tumor stroma model of cancer or 'battery-operated tumor growth': A simple solution to the autophagy paradox. Cell Cycle. 9:4297–4306. 2010. View Article : Google Scholar : PubMed/NCBI

126 

Salem AF, Whitaker-Menezes D, Lin Z, Martinez-Outschoorn UE, Tanowitz HB, Al-Zoubi MS, Howell A, Pestell RG, Sotgia F and Lisanti MP: Two-compartment tumor metabolism: Autophagy in the tumor microenvironment and oxidative mitochondrial metabolism (OXPHOS) in cancer cells. Cell Cycle. 11:2545–2556. 2012. View Article : Google Scholar : PubMed/NCBI

127 

Zhang W, Trachootham D, Liu J, Chen G, Pelicano H, Garcia-Prieto C, Lu W, Burger JA, Croce CM, Plunkett W, et al: Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nat Cell Biol. 14:276–286. 2012. View Article : Google Scholar : PubMed/NCBI

128 

Carmeliet P and Jain RK: Molecular mechanisms and clinical applications of angiogenesis. Nature. 473:298–307. 2011. View Article : Google Scholar : PubMed/NCBI

129 

Risau W: Mechanisms of angiogenesis. Nature. 386:671–674. 1997. View Article : Google Scholar : PubMed/NCBI

130 

Carmeliet P and Jain RK: Angiogenesis in cancer and other diseases. Nature. 407:249–257. 2000. View Article : Google Scholar : PubMed/NCBI

131 

Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J and Harris AL: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 56:4625–4629. 1996.PubMed/NCBI

132 

Polverini PJ and Leibovich SJ: Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest. 51:635–642. 1984.PubMed/NCBI

133 

O'Sullivan C, Lewis CE, Harris AL and McGee JO: Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet. 342:148–149. 1993. View Article : Google Scholar : PubMed/NCBI

134 

Lewis CE, Leek R, Harris A and McGee JO: Cytokine regulation of angiogenesis in breast cancer: The role of tumor-associated macrophages. J Leukoc Biol. 57:747–751. 1995.PubMed/NCBI

135 

Harmey JH, Dimitriadis E, Kay E, Redmond HP and Bouchier-Hayes D: Regulation of macrophage production of vascular endothelial growth factor (VEGF) by hypoxia and transforming growth factor beta-1. Ann Surg Oncol. 5:271–278. 1998. View Article : Google Scholar : PubMed/NCBI

136 

Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg JI, Cheresh DA and Johnson RS: Deletion of vascular endothelial growth factor in myeloid cells accelerates tumori-genesis. Nature. 456:814–818. 2008. View Article : Google Scholar : PubMed/NCBI

137 

Bingle L, Lewis CE, Corke KP, Reed MW and Brown NJ: Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br J Cancer. 94:101–107. 2006. View Article : Google Scholar : PubMed/NCBI

138 

Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, Dinarello CA and Apte RN: IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA. 100:2645–2650. 2003. View Article : Google Scholar : PubMed/NCBI

139 

Chen P, Huang Y, Bong R, Ding Y, Song N, Wang X, Song X and Luo Y: Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner. Clin Cancer Res. 17:7230–7239. 2011. View Article : Google Scholar : PubMed/NCBI

140 

Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A, Politi LS, Gentner B, Brown JL, Naldini L, et al: Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 19:512–526. 2011. View Article : Google Scholar : PubMed/NCBI

141 

Hughes R, Fang HY, Muthana M and Lewis CE: Role of tumour-associated macrophages in the regulation of angiogenesis. Tumour-Associated Macrophages. 17–29. 2011. View Article : Google Scholar

142 

Giraudo E, Inoue M and Hanahan D: An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 114:623–633. 2004. View Article : Google Scholar : PubMed/NCBI

143 

Li ZR, Li YP, Lin ML, Su WR, Zhang WX, Zhang Y, Yao L and Liang D: Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas. Cornea. 31:1028–1035. 2012. View Article : Google Scholar : PubMed/NCBI

144 

Houghton AM, Grisolano JL, Baumann ML, Kobayashi DK, Hautamaki RD, Nehring LC, Cornelius LA and Shapiro SD: Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases. Cancer Res. 66:6149–6155. 2006. View Article : Google Scholar : PubMed/NCBI

145 

Guo X, Oshima H, Kitmura T, Taketo MM and Oshima M: Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biol Chem. 283:19864–19871. 2008. View Article : Google Scholar : PubMed/NCBI

146 

Zhang Y, Tang H, Cai J, Zhang T, Guo J, Feng D and Wang Z: Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 303:47–55. 2011. View Article : Google Scholar : PubMed/NCBI

147 

Friedl P and Wolf K: Tumour-cell invasion and migration: Diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI

148 

Steeg PS: Tumor metastasis: Mechanistic insights and clinical challenges. Nat Med. 12:895–904. 2006. View Article : Google Scholar : PubMed/NCBI

149 

Valastyan S and Weinberg RA: Tumor metastasis: Molecular insights and evolving paradigms. Cell. 147:275–292. 2011. View Article : Google Scholar : PubMed/NCBI

150 

Liotta LA, Kleinerman J, Catanzaro P and Rynbrandt D: Degradation of basement membrane by murine tumor cells. J Natl Cancer Inst. 58:1427–1431. 1977.PubMed/NCBI

151 

Liotta LA: Tumor invasion and metastases - role of the extracellular matrix: Rhoads memorial Award lecture. Cancer Res. 46:1–7. 1986.PubMed/NCBI

152 

Fingleton B, Vargo-Gogola T, Crawford HC and Matrisian LM: Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia. 3:459–468. 2001. View Article : Google Scholar

153 

Noë V, Fingleton B, Jacobs K, Crawford HC, Vermeulen S, Steelant W, Bruyneel E, Matrisian LM and Mareel M: Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci. 114:111–118. 2001.

154 

Sameni M, Dosescu J, Moin K and Sloane BF: Functional imaging of proteolysis: Stromal and inflammatory cells increase tumor proteolysis. Mol Imaging. 2:159–175. 2003. View Article : Google Scholar : PubMed/NCBI

155 

Grimshaw MJ, Hagemann T, Ayhan A, Gillett CE, Binder C and Balkwill FR: A role for endothelin-2 and its receptors in breast tumor cell invasion. Cancer Res. 64:2461–2468. 2004. View Article : Google Scholar : PubMed/NCBI

156 

Sahai E: Mechanisms of cancer cell invasion. Curr Opin Genet Dev. 15:87–96. 2005. View Article : Google Scholar : PubMed/NCBI

157 

Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K and Sahai E: Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 9:1392–1400. 2007. View Article : Google Scholar : PubMed/NCBI

158 

Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG and Keely PJ: Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 4:382006. View Article : Google Scholar : PubMed/NCBI

159 

Provenzano PP, Inman DR, Eliceiri KW, Trier SM and Keely PJ: Contact guidance mediated three-dimensional cell migration is regulated by rho/rock-dependent matrix reorganization. Biophys J. 95:5374–5384. 2008. View Article : Google Scholar : PubMed/NCBI

160 

Goetz JG, Minguet S, Navarro-Lérida I, Lazcano JJ, Samaniego R, Calvo E, Tello M, Osteso-Ibáñez T, Pellinen T, Echarri A, et al: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 146:148–163. 2011. View Article : Google Scholar : PubMed/NCBI

161 

Chen J, Yao Y, Gong C, Yu F, Su S, Chen J, Liu B, Deng H, Wang F, Lin L, et al: CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PItPnm3. Cancer Cell. 19:541–555. 2011. View Article : Google Scholar : PubMed/NCBI

162 

Yamaguchi H, Pixley F and Condeelis J: Invadopodia and podosomes in tumor invasion. Eur J Cell Biol. 85:213–218. 2006. View Article : Google Scholar : PubMed/NCBI

163 

Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M, Segall J, Eddy R, Miki H, Takenawa T, et al: Molecular mechanisms of invadopodium formation: The role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 168:441–452. 2005. View Article : Google Scholar : PubMed/NCBI

164 

Buccione R, Orth JD and McNiven MA: Foot and mouth: Podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol. 5:647–657. 2004. View Article : Google Scholar : PubMed/NCBI

165 

Calle Y, Chou HC, Thrasher AJ and Jones GE: Wiskott-Aldrich syndrome protein and the cytoskeletal dynamics of dendritic cells. J Pathol. 204:460–469. 2004. View Article : Google Scholar : PubMed/NCBI

166 

Linder S and Aepfelbacher M: Podosomes: Adhesion hot-spots of invasive cells. Trends Cell Biol. 13:376–385. 2003. View Article : Google Scholar : PubMed/NCBI

167 

Mizutani K, Miki H, He H, Maruta H and Takenawa T: Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res. 62:669–674. 2002.PubMed/NCBI

168 

Moreno-Bueno G, Portillo F and Cano A: Transcriptional regulation of cell polarity in EMT and cancer. Oncogene. 27:6958–6969. 2008. View Article : Google Scholar : PubMed/NCBI

169 

Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI

170 

Liu R, Li J, Xie K, Zhang T, Lei Y, Chen Y, Zhang L, Huang K, Wang K, Wu H, et al: FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer. Cancer Res. 73:5926–5935. 2013. View Article : Google Scholar : PubMed/NCBI

171 

Bergers G, Song S, Meyer-Morse N, Bergsland E and Hanahan D: Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 111:1287–1295. 2003. View Article : Google Scholar : PubMed/NCBI

172 

Raza A, Franklin MJ and Dudek AZ: Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am J Hematol. 85:593–598. 2010. View Article : Google Scholar : PubMed/NCBI

173 

Cooke VG, LeBleu VS, Keskin D, Khan Z, O'Connell JT, Teng Y, Duncan MB, Xie L, Maeda G, Vong S, et al: Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell. 21:66–81. 2012. View Article : Google Scholar : PubMed/NCBI

174 

Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, Del Barrio MG, Portillo F and Nieto MA: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2:76–83. 2000. View Article : Google Scholar : PubMed/NCBI

175 

Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J and García De Herreros A: The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2:84–89. 2000. View Article : Google Scholar : PubMed/NCBI

176 

Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M and Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 6:931–940. 2004. View Article : Google Scholar : PubMed/NCBI

177 

Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM and Zhou BP: Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 15:416–428. 2009. View Article : Google Scholar : PubMed/NCBI

178 

Quigley JP and Armstrong PB: Tumor cell intravasation alucidated: The chick embryo opens the window. Cell. 94:281–284. 1998. View Article : Google Scholar : PubMed/NCBI

179 

Wyckoff JB, Jones JG, Condeelis JS and Segall JE: A critical step in metastasis: In vivo analysis of intravasation at the primary tumor. Cancer Res. 60:2504–2511. 2000.PubMed/NCBI

180 

Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, Simonavicius N, Schneider C, Lang M, Stürzl M, et al: Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPk pathway. Cancer Cell. 22:91–105. 2012. View Article : Google Scholar : PubMed/NCBI

181 

Gay LJ and Felding-Habermann B: Contribution of platelets to tumour metastasis. Nat Rev Cancer. 11:123–134. 2011. View Article : Google Scholar : PubMed/NCBI

182 

Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, et al: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 450:1235–1239. 2007. View Article : Google Scholar : PubMed/NCBI

183 

Huang YY, Hoshino K, Chen P, Wu CH, Lane N, Huebschman M, Liu H, Sokolov K, Uhr JW, Frenkel EP, et al: Immunomagnetic nanoscreening of circulating tumor cells with a motion controlled microfluidic system. Biomed Microdevices. 15:673–681. 2013. View Article : Google Scholar :

184 

Cai H and Peng F: 2-NBDG fluorescence imaging of hyper-metabolic circulating tumor cells in mouse xenograft model of breast cancer. J Fluoresc. 23:213–220. 2013. View Article : Google Scholar

185 

Nieswandt B, Hafner M, Echtenacher B and Männel DN: Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 59:1295–1300. 1999.PubMed/NCBI

186 

Mbeunkui F and Johann DJ Jr: Cancer and the tumor micro-environment: A review of an essential relationship. Cancer Chemother Pharmacol. 63:571–582. 2009. View Article : Google Scholar

187 

Gupta GP, Nguyen DX, Chiang AC, Bos PD, Kim JY, Nadal C, Gomis RR, Manova-Todorova K and Massagué J: Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature. 446:765–770. 2007. View Article : Google Scholar : PubMed/NCBI

188 

Psaila B, Kaplan RN, Port ER and Lyden D: Priming the 'soil' for breast cancer metastasis: The pre-metastatic niche. Breast Dis. 26:65–74. 2007.PubMed/NCBI

189 

Psaila B and Lyden D: The metastatic niche: Adapting the foreign soil. Nat Rev Cancer. 9:285–293. 2009. View Article : Google Scholar : PubMed/NCBI

190 

Hiratsuka S, Watanabe A, Aburatani H and Maru Y: Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol. 8:1369–1375. 2006. View Article : Google Scholar : PubMed/NCBI

191 

Rafii S and Lyden D: S100 chemokines mediate bookmarking of premetastatic niches. Nat Cell Biol. 8:1321–1323. 2006. View Article : Google Scholar : PubMed/NCBI

192 

Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H and Maru Y: The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 10:1349–1355. 2008. View Article : Google Scholar : PubMed/NCBI

193 

Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, et al: VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 438:820–827. 2005. View Article : Google Scholar : PubMed/NCBI

194 

Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, et al: Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell. 21:488–503. 2012. View Article : Google Scholar : PubMed/NCBI

195 

Roodhart JM, Daenen LG, Stigter EC, Prins HJ, Gerrits J, Houthuijzen JM, Gerritsen MG, Schipper HS, Backer MJ, van Amersfoort M, et al: Mesenchymal stem cells induce resistance to chemotherapy through the release of platinum-induced fatty acids. Cancer Cell. 20:370–383. 2011. View Article : Google Scholar : PubMed/NCBI

196 

Joosse SA and Pantel K: Tumor-educated platelets as liquid biopsy in cancer patients. Cancer Cell. 28:552–554. 2015. View Article : Google Scholar : PubMed/NCBI

197 

Wong HK, Fatimy RE, Onodera C, Wei Z, Yi M, Mohan A, Gowrisankaran S, Karmali P, Marcusson E, Wakimoto H, et al: The Cancer Genome Atlas Analysis predicts microRNA for targeting cancer growth and vascularization in glioblastoma. Mol Ther. 23:1234–1247. 2015. View Article : Google Scholar : PubMed/NCBI

198 

Resnick MJ, Lopatin M, Shore ND, Lam PN, Helfand B, Abramson RD, Crager M, Bonham M, Tezcan H, Clark-Langone KM, et al: Analysis of tumor DNA in urine as a highly sensitive liquid biopsy for patients with non-muscle invasive bladder cancer (NMIBC). Clin Cancer Res. 22:142016.

199 

Mishra RK, Wei C, Hresko RC, Bajpai R, Heitmeier M, Matulis SM, Nooka AK, Rosen ST, Hruz PW, Schiltz GE, et al: In Silico modeling-based identification of glucose transporter 4 (GLUT4)-selective inhibitors for cancer therapy. J Biol Chem. 290:14441–14453. 2015. View Article : Google Scholar : PubMed/NCBI

200 

Tuxhorn JA, McAlhany SJ, Yang F, Dang TD and Rowley DR: Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model. Cancer Res. 62:6021–6025. 2002.PubMed/NCBI

201 

Carmeliet P: Angiogenesis in health and disease. Nat Med. 9:653–660. 2003. View Article : Google Scholar : PubMed/NCBI

202 

Joyce JA, Freeman C, Meyer-Morse N, Parish CR and Hanahan D: A functional heparan sulfate mimetic implicates both heparanase and heparan sulfate in tumor angiogenesis and invasion in a mouse model of multistage cancer. Oncogene. 24:4037–4051. 2005. View Article : Google Scholar : PubMed/NCBI

203 

Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C, Hynes RO, Werb Z, Sudhakar A and Kalluri R: Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphav beta3 integrin. Cancer Cell. 3:589–601. 2003. View Article : Google Scholar : PubMed/NCBI

204 

Rudland PS, Platt-Higgins A, El-Tanani M, De Silva Rudland S, Barraclough R, Winstanley JH, Howitt R and West CR: Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 62:3417–3427. 2002.PubMed/NCBI

205 

El-Tanani MK, Campbell FC, Kurisetty V, Jin D, Mccann M and Rudland PS: The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev. 17:463–474. 2006. View Article : Google Scholar : PubMed/NCBI

206 

Tuck AB and Chambers AF: The role of osteopontin in breast cancer: Clinical and experimental studies. J Mammary Gland Biol Neoplasia. 6:419–429. 2001. View Article : Google Scholar

207 

Weber GF: The metastasis gene osteopontin: A candidate target for cancer therapy. Biochim Biophys Acta. 1552:61–85. 2001.

208 

Matarrese P, Fusco O, Tinari N, Natoli C, Liu FT, Semeraro ML, Malorni W and Iacobelli S: Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties. Int J Cancer. 85:545–554. 2000. View Article : Google Scholar : PubMed/NCBI

209 

Inohara H, Honjo Y, Yoshii T, Akahani S, Yoshida J, Hattori K, Okamoto S, Sawada T, Raz A and Kubo T: Expression of galectin-3 in fine-needle aspirates as a diagnostic marker differentiating benign from malignant thyroid neoplasms. Cancer. 85:2475–2484. 1999. View Article : Google Scholar : PubMed/NCBI

210 

Pinedo HM, Verheul HM, D'Amato RJ and Folkman J: Involvement of platelets in tumour angiogenesis? Lancet. 352:1775–1777. 1998. View Article : Google Scholar : PubMed/NCBI

211 

Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D and Tarnawski AS: Prostaglandin E2 transactivates EGF receptor: A novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 8:289–293. 2002. View Article : Google Scholar : PubMed/NCBI

212 

Ikushima H and Miyazono K: TGFbeta signalling: A complex web in cancer progression. Nat Rev Cancer. 10:415–424. 2010. View Article : Google Scholar : PubMed/NCBI

213 

Sierko E and Wojtukiewicz MZ: Platelets and angiogenesis in malignancy. Semin Thromb Hemost. 30:95–108. 2004. View Article : Google Scholar : PubMed/NCBI

214 

Medina VA and Rivera ES: Histamine receptors and cancer pharmacology. Br J Pharmacol. 161:755–767. 2010. View Article : Google Scholar : PubMed/NCBI

215 

Moghaddam A, Zhang HT, Fan TP, HU DE, Lees VC, Turley H, Fox SB, Gatter KC, Harris AL and Bicknell R: Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA. 92:998–1002. 1995. View Article : Google Scholar : PubMed/NCBI

216 

Bronckaers A, Gago F, Balzarini J and Liekens S: The dual role of thymidine phosphorylase in cancer development and chemotherapy. Med Res Rev. 29:903–953. 2009. View Article : Google Scholar : PubMed/NCBI

217 

Geiger TR and Peeper DS: Critical role for TrkB kinase function in anoikis suppression, tumorigenesis, and metastasis. Cancer Res. 67:6221–6229. 2007. View Article : Google Scholar : PubMed/NCBI

218 

Kim YJ, Borsig L, Varki NM and Varki A: P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci USA. 95:9325–9330. 1998. View Article : Google Scholar : PubMed/NCBI

219 

David M, Wannecq E, Descotes F, Jansen S, Deux B, Ribeiro J, Serre CM, Grès S, Bendriss-Vermare N, Bollen M, et al: Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts. PLoS One. 5:e97412010. View Article : Google Scholar : PubMed/NCBI

220 

Visentin B, Vekich JA, Sibbald BJ, Cavalli AL, Moreno KM, Matteo RG, Garland WA, Lu Y, Yu S, Hall HS, et al: Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell. 9:225–238. 2006. View Article : Google Scholar : PubMed/NCBI

221 

Ruf W and Mueller BM: Thrombin generation and the pathogenesis of cancer. Semin Thromb Hemost. 32(Suppl 1): 61–68. 2006. View Article : Google Scholar : PubMed/NCBI

222 

Bajou K, Noël A, Gerard RD, Masson V, Brunner N, Holst-Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, et al: Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med. 4:923–928. 1998. View Article : Google Scholar : PubMed/NCBI

223 

Falcón BL, Hashizume H, Koumoutsakos P, Chou J, Bready JV, Coxon A, Oliner JD and McDonald DM: Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels. Am J Pathol. 175:2159–2170. 2009. View Article : Google Scholar : PubMed/NCBI

224 

Payne AS and Cornelius LA: The role of chemokines in melanoma tumor growth and metastasis. J Invest Dermatol. 118:915–922. 2002. View Article : Google Scholar : PubMed/NCBI

225 

Wu Y, Li YY, Matsushima K, Baba T and Mukaida N: CCL3-CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process. J Immunol. 181:6384–6393. 2008. View Article : Google Scholar : PubMed/NCBI

226 

Läubli H, Spanaus KS and Borsig L: Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes. Blood. 114:4583–4591. 2009. View Article : Google Scholar : PubMed/NCBI

227 

Yi F, Jaffe R and Prochownik EV: The CCL6 chemokine is differentially regulated by c-Myc and L-Myc, and promotes tumorigenesis and metastasis. Cancer Res. 63:2923–2932. 2003.PubMed/NCBI

228 

Keeley EC, Mehrad B and Strieter RM: CXC chemokines in cancer angiogenesis and metastases. Adv Cancer Res. 106:91–111. 2010. View Article : Google Scholar : PubMed/NCBI

229 

Nakamura ES, Koizumi K, Kobayashi M, Saitoh Y, Arita Y, Nakayama T, Sakurai H, Yoshie O and Saiki I: RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4. Clin Exp Metastasis. 23:9–18. 2006. View Article : Google Scholar : PubMed/NCBI

230 

Romagnani P, Lasagni L, Annunziato F, Serio M and Romagnani S: CXC chemokines: The regulatory link between inflammation and angiogenesis. Trends Immunol. 25:201–209. 2004. View Article : Google Scholar : PubMed/NCBI

231 

Strieter RM, Burdick MD, Gomperts BN, Belperio JA and Keane MP: CXC chemokines in angiogenesis. Cytokine Growth Factor Rev. 16:593–609. 2005. View Article : Google Scholar : PubMed/NCBI

232 

Feliciano P: CXCL1 and CXCL2 link metastasis and chemoresistance. Nat Genet. 44:8402012.

233 

Keane MP, Belperio JA, Xue YY, Burdick MD and Strieter RM: Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer. J Immunol. 172:2853–2860. 2004. View Article : Google Scholar : PubMed/NCBI

234 

White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB and Arenberg DA: Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: Role in angiogenesis and prognosis. Clin Cancer Res. 9:853–860. 2003.PubMed/NCBI

235 

Strieter RM, Burdick MD, Mestas J, Gomperts B, Keane MP and Belperio JA: Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer. 42:768–778. 2006. View Article : Google Scholar : PubMed/NCBI

236 

Miyazaki H, Patel V, Wanzg H, Edmunzs RK, Gutkind JS and Yeudall WA: Down-regulation of CXCL5 inhibits squamous carcinogenesis. Cancer Res. 66:4279–4284. 2006. View Article : Google Scholar : PubMed/NCBI

237 

Gijsbers K, Gouwy M, Struyf S, Wuyts A, Proost P, Opdenakker G, Penninckx F, Ectors N, Geboes K and van Damme J: GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors. Exp Cell Res. 303:331–342. 2005. View Article : Google Scholar : PubMed/NCBI

238 

Verbeke H, Struyf S, Berghmans N, Van Coillie E, Opdenakker G, Uyttenhove C, Van Snick J and Van Damme J: Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis. Cancer Lett. 302:54–62. 2011. View Article : Google Scholar : PubMed/NCBI

239 

Tang Z, Yu M, Miller F, Berk RS, Tromp G and Kosir MA: Increased invasion through basement membrane by CXCL7-transfected breast cells. Am J Surg. 196:690–696. 2008. View Article : Google Scholar : PubMed/NCBI

240 

Bachelder RE, Wendt MA and Mercurio AM: Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res. 62:7203–7206. 2002.PubMed/NCBI

241 

Belperio JA, Phillips RJ, Burdick MD, Lutz M, Keane M and Strieter R: The SDF-1/CXCL 12/CXCR4 biological axis in non-small cell lung cancer metastases. Chest. 125(Suppl 5): 156S2004. View Article : Google Scholar : PubMed/NCBI

242 

Pan J, Mestas J, Burdick MD, Phillips RJ, Thomas GV, Reckamp K, Belperio JA and Strieter RM: Stromal derived factor-1 (SDF-1/CXCL12) and cXcr4 in renal cell carcinoma metastasis. Mol Cancer. 5:562006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yuan Y, Jiang Y, Sun C and Chen Q: Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncol Rep 35: 2499-2515, 2016.
APA
Yuan, Y., Jiang, Y., Sun, C., & Chen, Q. (2016). Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncology Reports, 35, 2499-2515. https://doi.org/10.3892/or.2016.4660
MLA
Yuan, Y., Jiang, Y., Sun, C., Chen, Q."Role of the tumor microenvironment in tumor progression and the clinical applications (Review)". Oncology Reports 35.5 (2016): 2499-2515.
Chicago
Yuan, Y., Jiang, Y., Sun, C., Chen, Q."Role of the tumor microenvironment in tumor progression and the clinical applications (Review)". Oncology Reports 35, no. 5 (2016): 2499-2515. https://doi.org/10.3892/or.2016.4660
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan Y, Jiang Y, Sun C and Chen Q: Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncol Rep 35: 2499-2515, 2016.
APA
Yuan, Y., Jiang, Y., Sun, C., & Chen, Q. (2016). Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncology Reports, 35, 2499-2515. https://doi.org/10.3892/or.2016.4660
MLA
Yuan, Y., Jiang, Y., Sun, C., Chen, Q."Role of the tumor microenvironment in tumor progression and the clinical applications (Review)". Oncology Reports 35.5 (2016): 2499-2515.
Chicago
Yuan, Y., Jiang, Y., Sun, C., Chen, Q."Role of the tumor microenvironment in tumor progression and the clinical applications (Review)". Oncology Reports 35, no. 5 (2016): 2499-2515. https://doi.org/10.3892/or.2016.4660
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