IL-32 promotes lung cancer cell invasion and metastasis through p38 MAPK signaling pathway: Cancer-associated fibroblast-derived

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Abstract

Lung cancer is the leading cause of cancer death in the United States and around the world. Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear.  In the present study, we investigated the role of interaction of interleukin 32 (IL-32) with integrin on the metastatic potential of lung cancer cells and related CAF pathway. We found that IL-32, an ‘RGD’ motif–containing cytokine, was found to be abundantly expressed in CAFs. Integrin β3 turned out to be up-regulated in non-small lung cancer (NSCLC) during epithelial–mesenchymal transition (EMT). CAF-derived IL-32 specifically bound to integrin β3 through the RGD motif, thus activating intracellular downstream p38 MAPK signalling in NSCLC cells. This signalling increased the expression of EMT markers and promoted tumor cell invasion. While, inhibition of IL-32 led to specific inactivation of p38 MAPK signalling in tumor cells. Furthermore, blockage of the p38 MAPK pathway also diminished IL-32-induced expression of EMT markers and NSCLC cell invasion and metastasis.

Keywords:NSCLC; MAPK; CAF; RGD

Copyright © 2018 by The American Society for BioMedicine and BM-Publisher, Inc.

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1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
https://doi.org/10.3322/caac.21262
PMid:25651787
2. Moon YW, Jeung HC, Rha SY, et al. Changing patterns of prognosticators during 15-year follow-up of advanced gastric cancer after radical gastrectomy and adjuvant chemotherapy: a 15-year follow-up study at a single korean institute. Annals of surgical oncology 2007;14:2730-2737.
https://doi.org/10.1245/s10434-007-9479-4
PMid:17632757
3. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nature reviews Cancer 2002;2:442-454.
https://doi.org/10.1038/nrc822
PMid:12189386
4. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental cell 2008;14:818-829.
https://doi.org/10.1016/j.devcel.2008.05.009
PMid:18539112
5. Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest 2009;119:1429-1437.
https://doi.org/10.1172/JCI36183
PMid:19487819 PMCid:PMC2689132
6. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-386.
https://doi.org/10.1002/ijc.29210
PMid:25220842
7. Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up‐regulation of FAK–PI 3 K/A kt pathway. Cell biology international 2014;38:85-91.
https://doi.org/10.1002/cbin.10184
PMid:24115647
8. Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008;359:1367-1380.
https://doi.org/10.1056/NEJMra0802714
PMid:18815398
9. Mego M, Mani SA, Cristofanilli M. Molecular mechanisms of metastasis in breast cancer—clinical applications. Nat Rev Clin Oncol 2010;7:693-701.
https://doi.org/10.1038/nrclinonc.2010.171
PMid:20956980
10. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013;19:1423-1437.
https://doi.org/10.1038/nm.3394
PMid:24202395 PMCid:PMC3954707
11. Augsten M. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol 2014;4:62.
https://doi.org/10.3389/fonc.2014.00062
PMid:24734219 PMCid:PMC3973916
12. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer 2016;16:582-598.
https://doi.org/10.1038/nrc.2016.73
PMid:27550820
13. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006;6:392-401.
https://doi.org/10.1038/nrc1877
PMid:16572188
14. Lohr M, Schmidt C, Ringel J, et al. Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res 2001;61:550-555.
PMid:11212248
15. Wang X, Yang S, Zheng E, Xiao P, Zheng-Yu Li. Interleukin-10 inhibits ovarian cancer cells growth via down regulation of inflammatory cytokine production. American Journal of BioMedicine 2014;2(8): 940-951.
16. Aoyagi Y, Oda T, Kinoshita T, Nakahashi C, Hasebe T, Ohkohchi N, Ochiai A. Overexpression of TGF-beta by infiltrated granulocytes correlates with the expression of collagen mRNA in pancreatic cancer. Br J Cancer 2004;91:1316-1326.
https://doi.org/10.1038/sj.bjc.6602141
PMid:15365564 PMCid:PMC2409911
17. Bronzert DA, Pantazis P, Antoniades HN, Kasid A, Davidson N, Dickson RB, Lippman ME. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines. Proc Natl Acad Sci U S A 1987;84:5763-5767.
https://doi.org/10.1073/pnas.84.16.5763
PMid:3039506 PMCid:PMC298943
18. Zhuang J, Lu Q, Shen B, Huang X, Shen L, Zheng X, Huang R, Yan J, Guo H. TGFbeta1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Scientific Rep 2015;5:11924.
https://doi.org/10.1038/srep11924
PMid:26152796 PMCid:PMC4495469
19. Kojima Y, Acar A, Eaton EN,et al. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A 2010;107:20009-20014.
https://doi.org/10.1073/pnas.1013805107
PMid:21041659 PMCid:PMC2993333
20. Fang WB, Mafuvadze B, Yao M, Zou A, Portsche M, Cheng N. TGF-beta negatively regulates CXCL1 chemokine expression in mammary fibroblasts through enhancement of Smad2/3 and suppression of HGF/c-Met signaling mechanisms. PLoS One 2015;10:e0135063.
https://doi.org/10.1371/journal.pone.0135063
PMid:26252654 PMCid:PMC4529193
21. Tsai C, Kim H, Adriennea J. Critical role of IL-32 invasion and metastasis of colonic cancer through upregulation of matrix metalloproteinase (MMP)-2. American Journal of BioMedicine 2018;6(10):661-684.
https://doi.org/10.18081/2333-5106/018-10/661-684
22. Taguchi A, Kawana K, Tomio K, Yamashita A, Isobe Y, Nagasaka K, Koga K, Inoue T, Nishida H, Kojima S, Adachi K, Matsumoto Y, Arimoto T, et al. Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo. PLoS One 2014;9:e89605.
https://doi.org/10.1371/journal.pone.0089605
PMid:24586907 PMCid:PMC3937340
23. Zheng X, Carstens JL, Kim J, et al. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015;527:525-530.
https://doi.org/10.1038/nature16064
PMid:26560028 PMCid:PMC4849281
24. Bae YK, Choi JE, Kang SH, Lee SJ. Epithelial-Mesenchymal Transition Phenotype Is Associated with Clinicopathological Factors That Indicate Aggressive Biological Behavior and Poor Clinical Outcomes in Invasive Breast Cancer. J Breast Cancer 2015;18:256-263.
https://doi.org/10.4048/jbc.2015.18.3.256
PMid:26472976 PMCid:PMC4600690
25. Gupta GP, Massague J. Cancer metastasis: building a framework. Cell 2006;127(4):679-695.
https://doi.org/10.1016/j.cell.2006.11.001
PMid:17110329
26. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002;2(8):563-572.
https://doi.org/10.1038/nrc865
PMid:12154349
27. Vitolo D, Ciocci L, Deriu G, et al. Laminin alpha2 chain-positive vessels and epidermal growth factor in lung neuroendocrine carcinoma: a model of a novel cooperative role of laminin-2 and epidermal growth factor in vessel neoplastic invasion and metastasis. Am J Pathol 2006;168(3):991-1003.
https://doi.org/10.2353/ajpath.2006.041310
PMid:16507913 PMCid:PMC1606521
28. Lam TK, Gallicchio L, Lindsley K, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev 2009;18(1):184-195.
https://doi.org/10.1158/1055-9965.EPI-08-0710
PMid:19124497 PMCid:PMC2735794
29. Wu X, Zhou QH, Xu K. Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol Sin 2009;30(5):501-512.
https://doi.org/10.1038/aps.2009.50
PMid:19417730 PMCid:PMC4002831
30. AI-Timimi AH, Yousif NG. Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: pathological correlation and prognostic indicators. American Journal of BioMedicine 2014;2(12):295-312.https://doi.org/10.18081/2333-5106/014-12/1229-1239

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Research Article
DOI: http://dx.doi.org/10.18081/2333-5106/018-10/685-697
American Journal of BioMedicine Volume 6, Issue 8, pages 685-697
Received April 11, 2018; accepted October 19, 2018; published October 31, 2018

How to cite this article
Shete S, Kim Q, Wu X, Wang X, Dong Q. IL-32 promotes lung cancer cell invasion and metastasis through p38 MAPK signaling pathway: Cancer-associated fibroblast-derived. American Journal of BioMedicine 2018;6(10):685-697.

Case report outline
1. Abstract
2. Keywords
3. Introduction
4. Methods
5. Results
6. Discussion
7. References