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Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway

  • Authors:
    • Shuhai Chen
    • Yuji Morine
    • Kazunori Tokuda
    • Shinichiro Yamada
    • Yu Saito
    • Masaaki Nishi
    • Tetsuya Ikemoto
    • Mitsuo Shimada
  • View Affiliations / Copyright

    Affiliations: Department of Digestive and Transplant Surgery, Tokushima University, Tokushima 770‑8503, Japan
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 59
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    Published online on: July 1, 2021
       https://doi.org/10.3892/ijo.2021.5239
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Abstract

Targeting the tumor stroma is an important strategy in cancer treatment. Cancer‑associated fibroblasts (CAFs) and tumor‑associated macrophages (TAMs) are two main components in the tumor microenvironment (TME) in hepatocellular carcinoma (HCC), which can promote tumor progression. Plasminogen activator inhibitor‑1 (PAI‑1) upregulation in HCC is predictive of unfavorable tumor behavior and prognosis. However, the crosstalk between cancer cells, TAMs and CAFs, and the functions of PAI‑1 in HCC remain to be fully investigated. In the present study, macrophage polarization and key paracrine factors were assessed during their interactions with CAFs and cancer cells. Cell proliferation, wound healing and Transwell and Matrigel assays were used to investigate the malignant behavior of HCC cells in vitro. It was found that cancer cells and CAFs induced the M2 polarization of TAMs by upregulating the mRNA expression levels of CD163 and CD206, and downregulating IL‑6 mRNA expression and secretion in the macrophages. Both TAMs derived from cancer cells and CAFs promoted HCC cell proliferation and invasion. Furthermore, PAI‑1 expression was upregulated in TAMs after being stimulated with CAF‑conditioned medium and promoted the malignant behavior of the HCC cells by mediating epithelial‑mesenchymal transition. CAFs were the main producer of C‑X‑C motif chemokine ligand 12 (CXCL12) in the TME and CXCL12 contributed to the induction of PAI‑1 secretion in TAMs. In conclusion, the results of the present study suggested that CAFs promoted the M2 polarization of macrophages and induced PAI‑1 secretion via CXCL12. Furthermore, it was found that PAI‑1 produced by the TAMs enhanced the malignant behavior of the HCC cells. Therefore, these factors may be targets for inhibiting the crosstalk between tumor cells, CAFs and TAMs.
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View References

1 

Metcalf KJ, Alazzeh A, Werb Z and Weaver VM: Leveraging microenvironmental synthetic lethalities to treat cancer. J Clin Invest. 131:e1437652021. View Article : Google Scholar

2 

Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Bejarano L, Jordāo MJ and Joyce JA: Therapeutic targeting of the tumor microenvironment. Cancer Discov. 11:933–959. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Comito G, Giannoni E, Segura CP, Barcellos-de-Souza P, Raspollini MR, Baroni G, Lanciotti M, Serni S and Chiarugi P: Cancer-associated fibroblasts and M2-polarized macrophages synergize during prostate carcinoma progression. Oncogene. 33:2423–2431. 2014. View Article : Google Scholar

5 

Andersson P, Yang Y, Hosaka K, Zhang Y, Fischer C, Braun H, Liu S, Yu G, Liu S, Beyaert R, et al: Molecular mechanisms of IL-33-mediated stromal interactions in cancer metastasis. JCI Insight. 3:e1223752018. View Article : Google Scholar

6 

Feng R, Morine Y, Ikemoto T, Imura S, Iwahashi S, Saito Y and Shimada M: Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction. Cell Commun Signal. 16:542018. View Article : Google Scholar : PubMed/NCBI

7 

Kang JI, Kim DH, Sung KW, Shim SM, Cha-Molstad H, Soung NK, Lee KH, Hwang J, Lee HG, Kwon YT and Kim BY: p62-Induced cancer-associated fibroblast activation via the nrf2-atf6 pathway promotes lung tumorigenesis. Cancers (Basel). 13:8642021. View Article : Google Scholar

8 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Wu Q, Zhou LY, Lv DD, Zhu X and Tang H: Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression. J Hematol Oncol. 12:532019. View Article : Google Scholar : PubMed/NCBI

10 

Higashino N, Koma YI, Hosono M, Takase N, Okamoto M, Kodaira H, Nishio M, Shigeoka M, Kakeji Y and Yokozaki H: Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma. Lab Invest. 99:777–792. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Hashimoto O, Yoshida M, Koma YI, Yanai T, Hasegawa D, Kosaka Y, Nishimura N and Yokozaki H: Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development. J Pathol. 240:211–223. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Yang X, Lin Y, Shi Y, Li B, Liu W, Yin W, Dang Y, Chu Y, Fan J and He R: Fap promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3-CCL2 signaling. Cancer Res. 76:4124–4135. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Allaoui R, Bergenfelz C, Mohlin S, Hagerling C, Salari K, Werb Z, Anderson RL, Ethier SP, Jirström K, Påhlman S, et al: Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers. Nat Commun. 7:130502016. View Article : Google Scholar : PubMed/NCBI

14 

Cho H, Seo Y, Loke KM, Kim SW, Oh SM, Kim JH, Soh J, Kim HS, Lee H, Kim J, et al: Cancer-stimulated cafs enhance monocyte differentiation and protumoral tam activation via il6 and GM-CSF secretion. Clin Cancer Res. 24:5407–5421. 2018. View Article : Google Scholar : PubMed/NCBI

15 

Ji J, Eggert T, Budhu A, Forgues M, Takai A, Dang H, Ye Q, Lee JS, Kim JH, Greten TF and Wang XW: Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma. Hepatology. 62:481–495. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Kubala MH and DeClerck YA: The plasminogen activator inhibitor-1 paradox in cancer: A mechanistic understanding. Cancer Metastasis Rev. 38:483–492. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Li SJ, Wei XH, Zhan XM, He JY, Zeng YQ, Tian XM, Yuan ST and Sun L: Adipocyte-derived leptin promotes PAI-1-mediated breast cancer metastasis in a STAT3/miR-34a dependent manner. Cancers (Basel). 12:38642020. View Article : Google Scholar

18 

Mashiko S, Kitatani K, Toyoshima M, Ichimura A, Dan T, Usui T, Ishibashi M, Shigeta S, Nagase S, Miyata T and Yaegashi N: Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer. Cancer Biol Ther. 16:253–260. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Muñoz-Galván S, Rivero M, Peinado-Serrano J, Martinez-Pérez J, Fernández-Fernández MC, Ortiz MJ, García-Heredia JM and Carnero A: PAI1 is a marker of bad prognosis in rectal cancer but predicts a better response to treatment with PIM inhibitor AZD1208. Cells. 9:10712020. View Article : Google Scholar :

20 

Fang H, Placencio VR and DeClerck YA: Protumorigenic activity of plasminogen activator inhibitor-1 through an antiapoptotic function. J Natl Cancer Inst. 104:1470–1484. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Placencio VR and DeClerck YA: Plasminogen activator inhibitor-1 in cancer: Rationale and insight for future therapeutic testing. Cancer Res. 75:2969–2974. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Jin Y, Liang ZY, Zhou WX and Zhou L: Expression, clinicopathologic and prognostic significance of plasminogen activator inhibitor 1 in hepatocellular carcinoma. Cancer Biomark. 27:285–293. 2020. View Article : Google Scholar

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

24 

Zhang J, Zhang Q, Lou Y, Fu Q, Chen Q, Wei T, Yang JQ, Tang J, Wang J, Chen Y, et al: Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment. Hepatology. 67:1872–1889. 2018. View Article : Google Scholar

25 

Dahlem C, Siow WX, Lopatniuk M, Tse WK, Kessler SM, Kirsch SH, Hoppstädter J, Vollmar AM, Müller R, Luzhetskyy A, et al: Thioholgamide A, a new anti-proliferative anti-tumor agent, modulates macrophage polarization and metabolism. Cancers (Basel). 12:12882020. View Article : Google Scholar

26 

Che Y, Wang JN, Li Y, Lu ZL, Huang JB, Sun SG, Mao SS, Lei YY, Zang RC, Sun N and He J: Cisplatin-activated PAI-1 secretion in the cancer-associated fibroblasts with paracrine effects promoting esophageal squamous cell carcinoma progression and causing chemoresistance. Cell Death Dis. 9:7592018. View Article : Google Scholar : PubMed/NCBI

27 

Oh JW, Olman M and Benveniste EN: CXCL12-mediated induction of plasminogen activator inhibitor-1 expression in human CXCR4 positive astroglioma cells. Biol Pharm Bull. 32:573–577. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Phillips RJ, Burdick MD, Lutz M, Belperio JA, Keane MP and Strieter RM: The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases. Am J Respir Crit Care Med. 167:1676–1686. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Yin ZL, Dong CY, Jiang KQ, Xu Z, Li R, Guo K, Shao SJ and Wang L: Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma. J Hematol Oncol. 12:1012019. View Article : Google Scholar : PubMed/NCBI

30 

Pham K, Huynh D, Le L, Delitto D, Yang L, Huang J, Kang Y, Steinberg MB, Li J, Zhang L, et al: E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. Cancer Lett. 491:132–145. 2020. View Article : Google Scholar : PubMed/NCBI

31 

Yan W, Liu X, Ma H, Zhang H, Song X, Gao L, Liang X and Ma C: Tim-3 fosters HCC development by enhancing TGF-β-mediated alternative activation of macrophages. Gut. 64:1593–1604. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG and Li MO: The cellular and molecular origin of tumor-associated macrophages. Science. 344:921–925. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Yin Z, Ma TT, Lin Y, Lu X, Zhang CZ, Chen S and Jian ZX: IL-6/STAT3 pathway intermediates M1/M2 macrophage polarization during the development of hepatocellular carcinoma. J Cell Biochem. 119:9419–9432. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Wang Q, He Z, Huang M, Liu T, Wang Y, Xu H, Duan H, Ma P, Zhang L, Zamvil SS, et al: Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α. Nat Commun. 9:5592018. View Article : Google Scholar

35 

Augsten M, Sjöberg E, Frings O, Vorrink SU, Frijhoff J, Olsson E, Borg A and Östman A: Cancer-associated fibroblasts expressing CXCL14 rely upon NOS1-derived nitric oxide signaling for their tumor-supporting properties. Cancer Res. 74:2999–3010. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Li X, Bu WH, Meng L, Liu XC, Wang SS, Jiang LM, Ren MS, Fan Y and Sun HC: CXCL12/CXCR4 pathway orchestrates CSC-like properties by CAF recruited tumor associated macrophage in OSCC. Exp Cell Res. 378:131–138. 2019. View Article : Google Scholar : PubMed/NCBI

37 

Murray PJ: Macrophage polarization. Annu Rev Physiol. 79:541–566. 2017. View Article : Google Scholar

38 

Huang CP, Liu LX and Shyr CR: Tumor-associated macrophages facilitate bladder cancer progression by increasing cell growth, migration, invasion and cytokine expression. Anticancer Res. 40:2715–2724. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al: Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 110:20212–20217. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Tan HX, Gong WZ, Zhou K, Xiao ZG, Hou FT, Huang T, Zhang L, Dong HY, Zhang WL, Liu Y and Huang ZC: CXCR4/TGF-β1 mediated hepatic stellate cells differentiation into carcinoma-associated fibroblasts and promoted liver metastasis of colon cancer. Cancer Biol Ther. 21:258–268. 2020. View Article : Google Scholar

41 

Giacoia EG, Miyake M, Lawton A, Goodison S and Rosser CJ: PAI-1 leads to G1-phase cell-cycle progression through cyclin D3/cdk4/6 upregulation. Mol Cancer Res. 12:322–334. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Liu SL, Wu XS, Li FN, Yao WY, Wu ZY, Dong P, Wang XF and Gong W: ERRα promotes pancreatic cancer progression by enhancing the transcription of PAI1 and activating the MEK/ERK pathway. Am J Cancer Res. 10:3622–3643. 2020.

43 

Chen Y, Kelm RJ Jr, Budd RC, Sobel BE and Schneider DJ: Inhibition of apoptosis and caspase-3 in vascular smooth muscle cells by plasminogen activator inhibitor type-1. J Cell Biochem. 92:178–188. 2004. View Article : Google Scholar : PubMed/NCBI

44 

Wei X, Li S, He J, Du H, Liu Y, Yu W, Hu H, Han L, Wang C, Li H, et al: Tumor-secreted PAI-1 promotes breast cancer metastasis via the induction of adipocyte-derived collagen remodeling. Cell Commun Signal. 17:582019. View Article : Google Scholar : PubMed/NCBI

45 

Liu J, Chen Z, Huang M, Tang S, Wang Q, Hu P, Gupta P, Ashby CR Jr, Chen ZS and Zhang L: Plasminogen activator inhibitor (PAI) trap3, an exocellular peptide inhibitor of PAI-1, attenuates the rearrangement of F-actin and migration of cancer cells. Exp Cell Res. 391:1119872020. View Article : Google Scholar : PubMed/NCBI

46 

Chen S, Kang X, Liu G, Zhang B, Hu X and Feng Y: α7-Nicotinic acetylcholine receptor promotes cholangiocarcinoma progression and epithelial-mesenchymal transition process. Dig Dis Sci. 64:2843–2853. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Pal M, Bhattacharya S, Kalyan G and Hazra S: Cadherin profiling for therapeutic interventions in epithelial mesenchymal transition (EMT) and tumorigenesis. Exp Cell Res. 368:137–146. 2018. View Article : Google Scholar : PubMed/NCBI

48 

Yang JD, Ma L and Zhu Z: SERPINE1 as a cancer-promoting gene in gastric adenocarcinoma: Facilitates tumour cell proliferation, migration, and invasion by regulating EMT. J Chemother. 31:408–418. 2019. View Article : Google Scholar : PubMed/NCBI

49 

Lin X, Lin BW, Chen XL, Zhang BL, Xiao XJ, Shi JS, Lin JD and Chen X: PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in non-small cell lung cancer. Biochem Biophys Res Commun. 493:1464–1470. 2017. View Article : Google Scholar : PubMed/NCBI

50 

Hennan JK, Morgan GA, Swillo RE, Antrilli TM, Mugford C, Vlasuk GP, Gardell SJ and Crandall DL: Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. J Thromb Haemost. 6:1558–1564. 2008.PubMed/NCBI

51 

Gomes-Giacoia E, Miyake M, Goodison S and Rosser CJ: Targeting plasminogen activator inhibitor-1 inhibits angiogenesis and tumor growth in a human cancer xenograft model. Mol Cancer Ther. 12:2697–2708. 2013. View Article : Google Scholar : PubMed/NCBI

52 

Masuda T, Hattori N, Senoo T, Akita S, Ishikawa N, Fujitaka K, Haruta Y, Murai H and Kohno N: SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor progression and angiogenesis. Mol Cancer Ther. 12:2378–2388. 2013. View Article : Google Scholar : PubMed/NCBI

53 

Masuda T, Nakashima T, Namba M, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, Miyata Y, et al: Inhibition of PAI-1 limits chemotherapy resistance in lung cancer through suppressing myofibroblast characteristics of cancer-associated fibroblasts. J Cell Mol Med. 23:2984–2994. 2019. View Article : Google Scholar : PubMed/NCBI

54 

Kubala MH, Punj V, Placencio-Hickok VR, Fang H, Fernandez GE, Sposto R and DeClerck YA: Plasminogen activator inhibitor-1 promotes the recruitment and polarization of macrophages in cancer. Cell Rep. 25:2177–2191. 2018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen S, Morine Y, Tokuda K, Yamada S, Saito Y, Nishi M, Ikemoto T and Shimada M: Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway. Int J Oncol 59: 59, 2021.
APA
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M. ... Shimada, M. (2021). Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway. International Journal of Oncology, 59, 59. https://doi.org/10.3892/ijo.2021.5239
MLA
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M., Ikemoto, T., Shimada, M."Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway". International Journal of Oncology 59.2 (2021): 59.
Chicago
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M., Ikemoto, T., Shimada, M."Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway". International Journal of Oncology 59, no. 2 (2021): 59. https://doi.org/10.3892/ijo.2021.5239
Copy and paste a formatted citation
x
Spandidos Publications style
Chen S, Morine Y, Tokuda K, Yamada S, Saito Y, Nishi M, Ikemoto T and Shimada M: Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway. Int J Oncol 59: 59, 2021.
APA
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M. ... Shimada, M. (2021). Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway. International Journal of Oncology, 59, 59. https://doi.org/10.3892/ijo.2021.5239
MLA
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M., Ikemoto, T., Shimada, M."Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway". International Journal of Oncology 59.2 (2021): 59.
Chicago
Chen, S., Morine, Y., Tokuda, K., Yamada, S., Saito, Y., Nishi, M., Ikemoto, T., Shimada, M."Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway". International Journal of Oncology 59, no. 2 (2021): 59. https://doi.org/10.3892/ijo.2021.5239
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