STAT3 suppress the proliferation and invasion of ovarian cancer cells via IL-37 expression

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Research Article
Journal of Cellular Cancer  Volume 7, Issue 1, pages 43-56
Published: June 22, 2015


Mark Fullerton, Lihua Li, Ling Wu, David B. Mulier, Xian Chen, Celeste B. Determan, Jean Friese, Ling Yao

Abstract

Most ovarian cancers are highly invasive and the high burden of metastatic disease make them a leading cause of mortality among all women malignancies. The status of STAT3 signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of IL-37 was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of STAT3 on invasion/motility was checked by matrigel invasion and wound healing assay and Western blotting was used for protein detection. In this paper, we found IL-37 inhibited STAT3 expression and silecing STAT3 decreased significantly the ability of IL-37 to suppress cell proliferation and invasion of ovarian cancer cells. Collectively, our data link the STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of proinflammatory cytokines. Moreover, these results provide further support for the importance of these pathways as potential therapeutic targets in ovarian cancer cell.

Keywords: ovarian cancers; STAT3; IL-37; Metastatic disease; Invasion

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  1. Dinarello CA, Bufler P. Interleukin-37. Semin Immunol 2013;25(6):466–468. [PubMed]
  2. Gao W, Kumar S, Lotze MT, et al. Innate Immunity Mediated by the Cytokine IL-1 Homologue 4(IL-1H4/IL-1F7) Induces IL-12-Dependent Adaptive and Profound Antitumor Immunity. J. Immunol. 2003;170:107-13
  3. Zhao JJ, Pan QZ, Pan K, et al. Interleukin-37 mediates the antitumor activity in hepatocellular carcinoma:role for CD57+ NK cells. Sci Rep. 2014;4:5177-85.
  4. Nold MF, et al. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol 2010;11(11):1014–1022. [PubMed]
  5. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 2008; 269:199–225. [PubMed]
  6. Bufler P, Azam T, Gamboni-Robertson F, et al. A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity. Proc Natl Acad Sci USA 2002;99:13723–13728. [PubMed]
  7. Sushma M, Vamsikrishna B, Babu M M, et al. A review on role of Human Papilomma Virus (HPV) in cervical cancer. Pharma Tutor. 2014;2:21-30.
  8. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009; 9: 302–312. [PubMed]
  9. McNamee EN, Masterson JC, Jedlicka P, et al. Interleukin 37 expression protects mice from colitis. Proc Natl Acad Sci USA 2011;108(40):16711–16716. [PubMed]
  10. Konnikova L, Simeone MC, Kruger MM, et al. Signal transducer and activator of transcription 3 (STAT3) regulates human telomerase reverse transcriptase (hTERT) expression in human cancer and primary cells. Cancer Res. 2005;65:6516-20.
  11. Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479–490. [PubMed]
  12. Luo Y, Cai X, Liu S, et al. Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells. Proc Natl Acad Sci USA  2014;111(42):15178–15183. [PubMed]
  13. Tse C, Xiang RH, Bracht T, Naylor SL. Human semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res. 2002;62:542–6. [PubMed]
  14. Wang S, Pang T, Gao M, et al. HPV E6 induces eIF4E transcription to promote the proliferation and migration of cervical cancer. Febs Lett 2013;587:690-7.
  15. Dan G. WangDG, Yousif NG, Sadiq AM, Schilling MM, Danielson AJJ. Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell. American Journal of BioMedicine 2014; 2(3):292–305. [Abstract/Full-Text]
  16. Atwal JK, Singh KK, Tessier-Lavigne M, Miller FD, Kaplan DR. Semaphorin 3F antagonizes neurotrophin-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase signaling: a mechanism for growth cone collapse. J Neurosci 2003; 23:7602–9. [PubMed]
  17. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9:798-809.
  18. Bulau AM, et al. Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci USA 2014;111(7):2650–2655. [PubMed]
  19. Rieger J, Wick W, Weller M. Human malignant glioma cells express semaphorins and their receptors, neuropilins and plexins. Glia. 2003; 42:379–89. [PubMed]
  20. Yu H, Lee H, Herrmann A, et al. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat Rev Cancer 2014;14:736-46.
  21. Leoni F, Fossati G, Lewis EC, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med 2005;11(1-12):1–15. [PubMed]
  22. Boraschi D, Tagliabue A. The interleukin-1 receptor family. Semin Immunol 2013;25(6):394–407. [PubMed]
  23. Yang Y, Zhang ZX, Lian D, Haig A, Bhattacharjee RN, Jevnikar AM. IL-37 inhibits IL-18-induced tubular epithelial cell expression of pro-inflammatory cytokines and renal ischemia-reperfusion injury. Kidney Int 2015;87(2):396-408. [PubMed]

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Mark Fullerton, Lihua Li, Ling Wu, David B. Mulier, Xian Chen, Celeste B. Determan, Jean Friese, Ling Yao. STAT3 suppress the proliferation and invasion of ovarian cancer cells via IL-37 expression. Journal of cellular cancer 2014; 7(1):43-56.