Mesenchymal stem cells in the tumor microenvironment (Review)

Guan,Jian; Chen,Jie

doi:10.3892/br.2013.103

Mesenchymal stem cells in the tumor microenvironment (Review)

Authors:
- Jian Guan
- Jie Chen
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Affiliations: Department of Pathology, Peking Union Medical College Hospital, Beijing 100730, P.R. China
Published online on: May 10, 2013 https://doi.org/10.3892/br.2013.103
Pages: 517-521

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Abstract

Mesenchymal stem cells (MSCs) are non‑hematopoietic, multipotent cells, which are able to differentiate to bone, adipose and cartilage tissue. MSCs have the characteristic of migration to injured areas or tumor microenvironment following induction by chemokines or inflammatory factors. An increasing number of studies have reported that MSCs recruited to the tumor microenvironment play various roles in tumor cell development and tumor progression. In this study, we reviewed the studies related to the tumor‑promoting roles of MSCs from several aspects, such as increasing stemness of tumor cells, mediating migration, promoting angiogenesis, suppressing immune response and inducing drug resistance.

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1.	Jiang Y, Jahagirdar BN, Reinhardt RL, et al: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 418:41–49. 2002. View Article : Google Scholar : PubMed/NCBI
2.	Bianco P, Robey PG and Simmons PJ: Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell. 2:313–319. 2008. View Article : Google Scholar : PubMed/NCBI
3.	Dominici M, Le Blanc K, Mueller I, et al: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8:315–317. 2006. View Article : Google Scholar
4.	Tropel P, Noel D, Platet N, Legrand P, Benabid AL and Berger F: Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 295:395–406. 2004. View Article : Google Scholar : PubMed/NCBI
5.	Zuk PA, Zhu M, Mizuno H, et al: Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7:211–228. 2001. View Article : Google Scholar : PubMed/NCBI
6.	Jones EA, English A, Henshaw K, et al: Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum. 50:817–827. 2004. View Article : Google Scholar
7.	Williams JT, Southerland SS, Souza J, Calcutt AF and Cartledge RG: Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg. 65:22–26. 1999.PubMed/NCBI
8.	Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ and Andreeff M: Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res. 62:3603–3608. 2002.PubMed/NCBI
9.	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
10.	Tu S, Bhagat G, Cui G, et al: Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 14:408–419. 2008. View Article : Google Scholar : PubMed/NCBI
11.	Quante M, Tu SP, Tomita H, et al: Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 19:257–272. 2011. View Article : Google Scholar : PubMed/NCBI
12.	Gao H, Priebe W, Glod J and Banerjee D: Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells. 27:857–865. 2009. View Article : Google Scholar
13.	Direkze NC, Hodivala-Dilke K, Jeffery R, et al: Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 64:8492–8495. 2004. View Article : Google Scholar : PubMed/NCBI
14.	Zhang L, Tang A, Zhou Y, et al: Tumor-conditioned mesenchymal stem cells display hematopoietic differentiation and diminished influx of Ca²⁺. Stem Cells Dev. 21:1418–1428. 2012. View Article : Google Scholar : PubMed/NCBI
15.	Zhou Y, Guan X, Wang H, et al: Hypoxia induces osteogenic/angiogenic responses of bone marrow-derived mesenchymal stromal cells seeded on bone-derived scaffolds via ERK1/2 and p38 pathways. Biotechnol Bioeng. Jan 7–2013.(Epub ahead of print).
16.	Janeczek Portalska K, Leferink A, Groen N, et al: Endothelial differentiation of mesenchymal stromal cells. PLoS One. 7:e468422012.PubMed/NCBI
17.	Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, et al: Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res. 68:4331–4339. 2008. View Article : Google Scholar : PubMed/NCBI
18.	Zuk PA, Zhu M, Ashjian P, et al: Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 13:4279–4295. 2002.PubMed/NCBI
19.	Mosna F, Sensebé L and Krampera M: Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev. 19:1449–1470. 2010.
20.	Kidd S, Spaeth E, Watson K, et al: Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS One. 7:e305632012. View Article : Google Scholar : PubMed/NCBI
21.	Song S, Ewald AJ, Stallcup W, Werb Z and Bergers G: PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol. 7:870–879. 2005.
22.	McGrail DJ, Ghosh D, Quach ND and Dawson MR: Differential mechanical response of mesenchymal stem cells and fibroblasts to tumor-secreted soluble factors. PLoS One. 7:e332482012. View Article : Google Scholar : PubMed/NCBI
23.	Wang D, Park JS, Chu JS, et al: Proteomic profiling of bone marrow mesenchymal stem cells upon transforming growth factor beta1 stimulation. J Biol Chem. 279:43725–43734. 2004. View Article : Google Scholar : PubMed/NCBI
24.	Jotzu C, Alt E, Welte G, et al: Adipose tissue-derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor-derived factors. Anal Cell Pathol (Amst). 33:61–79. 2010. View Article : Google Scholar
25.	Heo SC, Lee KO, Shin SH, et al: Periostin mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in a xenograft lung adenocarcinoma model. Biochim Biophys Acta. 1813:2061–2070. 2011. View Article : Google Scholar : PubMed/NCBI
26.	Shinagawa K, Kitadai Y, Tanaka M, et al: Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer. Int J Cancer. 132:813–823. 2012. View Article : Google Scholar
27.	Cho JA, Park H, Lim EH and Lee KW: Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J Oncol. 40:130–138. 2012.PubMed/NCBI
28.	Lis R, Touboul C, Raynaud CM, et al: Mesenchymal cell interaction with ovarian cancer cells triggers pro-metastatic properties. PLoS One. 7:e383402012. View Article : Google Scholar : PubMed/NCBI
29.	Yan XL, Fu CJ, Chen L, et al: Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway. Breast Cancer Res Treat. 132:153–164. 2012. View Article : Google Scholar : PubMed/NCBI
30.	Klopp AH, Lacerda L, Gupta A, et al: Mesenchymal stem cells promote mammosphere formation and decrease E-cadherin in normal and malignant breast cells. PLoS One. 5:e121802010. View Article : Google Scholar : PubMed/NCBI
31.	Liu S, Ginestier C, Ou SJ, et al: Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res. 71:614–624. 2011. View Article : Google Scholar : PubMed/NCBI
32.	McLean K, Gong Y, Choi Y, et al: Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest. 121:3206–3219. 2011. View Article : Google Scholar : PubMed/NCBI
33.	Nishimura K, Semba S, Aoyagi K, Sasaki H and Yokozaki H: Mesenchymal stem cells provide an advantageous tumor microenvironment for the restoration of cancer stem cells. Pathobiology. 79:290–306. 2012. View Article : Google Scholar : PubMed/NCBI
34.	Hsu HS, Lin JH, Hsu TW, et al: Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway. Lung Cancer. 75:167–177. 2012. View Article : Google Scholar : PubMed/NCBI
35.	Tsai KS, Yang SH, Lei YP, et al: Mesenchymal stem cells promote formation of colorectal tumors in mice. Gastroenterology. 141:1046–1056. 2011. View Article : Google Scholar : PubMed/NCBI
36.	Li HJ, Reinhardt F, Herschman HR and Weinberg RA: Cancer-stimulated mesenchymal stem cells create a carcinoma stem-cell niche via prostaglandin E2 signaling. Cancer Discov. 2:840–855. 2012. View Article : Google Scholar : PubMed/NCBI
37.	Thiery JP: Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol. 15:740–746. 2003. View Article : Google Scholar : PubMed/NCBI
38.	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI
39.	El-Haibi CP, Bell GW, Zhang J, et al: Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy. Proc Natl Acad Sci USA. 109:17460–17465. 2012. View Article : Google Scholar : PubMed/NCBI
40.	Xu Q, Wang L, Li H, et al: Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β. Int J Oncol. 41:959–968. 2012.PubMed/NCBI
41.	Bhattacharya SD, Mi Z, Talbot LJ, Guo H and Kuo PC: Human mesenchymal stem cell and epithelial hepatic carcinoma cell lines in admixture: concurrent stimulation of cancer-associated fibroblasts and epithelial-to-mesenchymal transition markers. Surgery. 152:449–454. 2012. View Article : Google Scholar
42.	Jing Y, Han Z, Liu Y, et al: Mesenchymal stem cells in inflammation microenvironment accelerates hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition. PLoS One. 7:e432722012. View Article : Google Scholar
43.	Kabashima-Niibe A, Higuchi H, Takaishi H, et al: Mesenchymal stem cells regulate epithelial-to-mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer Sci. 104:157–164. 2012. View Article : Google Scholar
44.	Halpern JL, Kilbarger A and Lynch CC: Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 308:91–99. 2011. View Article : Google Scholar : PubMed/NCBI
45.	Rhodes LV, Antoon JW, Muir SE, Elliott S, Beckman BS and Burow ME: Effects of human mesenchymal stem cells on ER-positive human breast carcinoma cells mediated through ER-SDF-1/CXCR4 crosstalk. Mol Cancer. 9:2952010. View Article : Google Scholar : PubMed/NCBI
46.	Gallo M, De Luca A, Lamura L and Normanno N: Zoledronic acid blocks the interaction between mesenchymal stem cells and breast cancer cells: implications for adjuvant therapy of breast cancer. Ann Oncol. 23:597–604. 2012. View Article : Google Scholar : PubMed/NCBI
47.	Karnoub AE, Dash AB, Vo AP, et al: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449:557–563. 2007. View Article : Google Scholar : PubMed/NCBI
48.	Ye H, Cheng J, Tang Y, et al: Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to progression and metastasis of prostate cancer. Cancer Invest. 30:513–518. 2012. View Article : Google Scholar : PubMed/NCBI
49.	Beckermann BM, Kallifatidis G, Groth A, et al: VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 99:622–631. 2008. View Article : Google Scholar : PubMed/NCBI
50.	Suzuki K, Sun R, Origuchi M, et al: Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med. 17:579–587. 2011. View Article : Google Scholar : PubMed/NCBI
51.	Comsa S, Ciuculescu F and Raica M: Mesenchymal stem cell-tumor cell cooperation in breast cancer vasculogenesis. Mol Med Rep. 5:1175–1180. 2012.PubMed/NCBI
52.	Liu Y, Han ZP, Zhang SS, et al: Effects of inflammatory factors on mesenchymal stem cells and their role in the promotion of tumor angiogenesis in colon cancer. J Biol Chem. 286:25007–25015. 2011. View Article : Google Scholar : PubMed/NCBI
53.	Zhu W, Huang L, Li Y, et al: Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 315:28–37. 2012. View Article : Google Scholar : PubMed/NCBI
54.	Krampera M, Glennie S, Dyson J, et al: Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood. 101:3722–3729. 2003. View Article : Google Scholar : PubMed/NCBI
55.	Tabera S, Perez-Simon JA, Diez-Campelo M, et al: The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica. 93:1301–1309. 2008. View Article : Google Scholar : PubMed/NCBI
56.	Jiang XX, Zhang Y, Liu B, et al: Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood. 105:4120–4126. 2005. View Article : Google Scholar : PubMed/NCBI
57.	Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R and Fibbe WE: Mesenchymal stem cells inhibit generation and function of both CD34⁺-derived and monocyte-derived dendritic cells. J Immunol. 177:2080–2087. 2006. View Article : Google Scholar : PubMed/NCBI
58.	Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN and Papamichail M: Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells. 24:74–85. 2006. View Article : Google Scholar : PubMed/NCBI
59.	Spaggiari GM and Moretta L: Cellular and molecular interactions of mesenchymal stem cells in innate immunity. Immunol Cell Biol. 91:27–31. 2013. View Article : Google Scholar : PubMed/NCBI
60.	Batten P, Sarathchandra P, Antoniw JW, et al: Human mesenchymal stem cells induce T cell anergy and downregulate T cell allo-responses via the TH2 pathway: relevance to tissue engineering human heart valves. Tissue Eng. 12:2263–2273. 2006. View Article : Google Scholar : PubMed/NCBI
61.	Casiraghi F, Perico N and Remuzzi G: Mesenchymal stromal cells to promote solid organ transplantation tolerance. Curr Opin Organ Transplant. 18:51–58. 2013. View Article : Google Scholar : PubMed/NCBI
62.	Reinders ME, de Fijter JW, Roelofs H, et al: Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med. 2:107–111. 2013. View Article : Google Scholar
63.	Groh ME, Maitra B, Szekely E and Koc ON: Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol. 33:928–934. 2005. View Article : Google Scholar : PubMed/NCBI
64.	Sato K, Ozaki K, Oh I, et al: Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood. 109:228–234. 2007. View Article : Google Scholar : PubMed/NCBI
65.	Meisel R, Zibert A, Laryea M, Gobel U, Daubener W and Dilloo D: Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood. 103:4619–4621. 2004. View Article : Google Scholar : PubMed/NCBI
66.	Aggarwal S and Pittenger MF: Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 105:1815–1822. 2005. View Article : Google Scholar : PubMed/NCBI
67.	Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M and Rameshwar P: Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol. 184:5885–5894. 2010. View Article : Google Scholar : PubMed/NCBI
68.	Han Z, Tian Z, Lv G, et al: Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells. J Cell Mol Med. 15:2343–2352. 2011. View Article : Google Scholar : PubMed/NCBI
69.	Cheng J, Li L, Liu Y, Wang Z, Zhu X and Bai X: Interleukin-1α induces immunosuppression by mesenchymal stem cells promoting the growth of prostate cancer cells. Mol Med Rep. 6:955–960. 2012.
70.	Meads MB, Gatenby RA and Dalton WS: Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer. 9:665–674. 2009. View Article : Google Scholar : PubMed/NCBI
71.	Sanchez CG, Penfornis P, Oskowitz AZ, et al: Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis. 32:964–972. 2011. View Article : Google Scholar : PubMed/NCBI
72.	De Boeck A, Pauwels P, Hensen K, et al: Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut. 62:550–560. 2013.PubMed/NCBI
73.	Roodhart JM, Daenen LG, Stigter EC, 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