Ascites IL-10 Promotes Ovarian Cancer Cell Migration
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Ovarian cancer (OC) ascites is an inflammatory and immunosuppressive tumor environment characterized by the presence of various cytokines, chemokines and growth factors. The presence of high concentrations of these cytokines/chemokines in ascites is associated with a more aggressive tumor phenotype. IL-10 is an immunosuppressive cytokine for which high expression has been associated with poor prognosis in some cancers. However, its role on OC tumor cells has not been explored. Therefore, the aim of the current study was to elucidate the role of ascites IL-10 on the proliferation, migration and survival of OC cell lines. Here, we show that IL-10 levels are markedly increased in patients with advanced serous OC ascites relative to serous stage I/II ascites and peritoneal effusions from women with benign conditions. Ascites and IL-10 dose-dependently enhanced the proliferation and migration of OC cell lines CaOV3 and OVCAR3 but had no effect on cell survival. IL-10 levels in ascites positively correlated with the ability of ascites to promote cell migration but not proliferation. Depletion of IL-10 from ascites markedly inhibited ascites-induced OC cell migration but was not crucial for ascites-mediated cell proliferation. Taken together, our findings establish an important role for IL-10, as a component of ascites, in the migration of tumor cells.
KeywordsOvarian carcinoma Ascites IL-10 Cell migration Cell proliferation
This work was supported by funds from the Canadian Institute for Health Research (MOP-244194-CPT-CFDA-48852), the Centre de Recherche Clinique Étienne-Lebel du Centre Hospitalier Universitaire de Sherbrooke and the Université de Sherbrooke. Tumor banking were supported by the Banque de tissus et données of the Réseau de recherche sur le cancer of the Fond de recherche du Québec en Santé (FRQS) and Cancer de l’Ovaire Canada, associated with the Canadian Tumor Repository Network (CTRNet). The tissue bank provided malignant ascites and peritoneal fluids.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
- 8.Giuntoli RL, Webb TJ, Zoso A, Rogers O, Diaz-Montes TP, Bristow RE, Oelke M (2009) Ovarian cancer-associated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Res 29:2875–2884Google Scholar
- 16.Puiffe ML, Le Page C, Filali-Mouhim A, Zietarska M, Ouellet V, Tonin PN, Chevrette M, Provencher DM, Mes-Masson AM (2007) Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia 9:820–829CrossRefPubMedGoogle Scholar
- 20.Jankovic D, Kullberg MC, Feng CG, Goldszmid RS, Collazo CM, Wilson M, Wynn TA, Kamanaka M, Flavell RA, Sher A (2007) Conventional T-bet(+) Foxp3(−) Th1 cells are the major source of host protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204:273–283CrossRefPubMedGoogle Scholar
- 24.Li C, Li H, Jiang K, Li J, Gai X (2014) TLR4 signaling pathway in mouse Lewis lung cancer cells promotes the expression of TGF-β1 and IL-10 and tumor cells migration. Biomed Mater Eng 24:869–875Google Scholar
- 27.Boyano MD, Garcia-Vazquez MD, Lopez-Michelena T, Gardeazabal J, Bilbao J, Canavate M, Galdeano AG, Izu R, Diaz-Ramon L, Raton JA, Diaz-Perez JL (2000) Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma. Br J Cancer 83:847–852CrossRefPubMedGoogle Scholar
- 31.Boulland ML, Meignin V, Leroy-Viard K, Copie-Bergman C, Brière J, Touitou R, Kanavaros P, Gaulard P (1998) Human interleukin-10 expression in T/natural killer-cell lymphomas: association with anaplastic large cell lymphomas and nasal natural killer-cell lymphomas. Am J Pathol 153:1229–1237CrossRefPubMedGoogle Scholar
- 32.Nowark M, Glowacka E, Szpakowski M, Szyllo K, Malinowski A, Kulig A, Tchorzewski H, Wilczynski J (2010) Proinflammatory and immunosuppressive serum, ascites and cyst fluid cytokines in patients with early and advanced ovarian cancer and benign ovarian tumors. Neuro Endocrinol Lett 31:375–383Google Scholar
- 34.Mustea A, Konsgen D, Braicu EI, Pirvulescu C, Sun P, Sofroni D, Lichtenegger W, Sehouli J (2006) Expression of IL-10 in patients with ovarian carcinoma. Anticancer Res 26:1715–1718Google Scholar
- 37.Brencicova E, Jagger AL, Evans HG, Georgouli M, Laios AH, Montalto S, Mehra G, Spencer J, Ahmed AA, Raju-Kankipati S, Taams LS, Diebold SS (2017) Interleukin-10 and prostaglandin E2 have complementary but distinct suppressive effects on toll-like receptor-mediated dendritic cell activation in ovarian carcinoma. PLoS One 12:e0175712CrossRefPubMedGoogle Scholar
- 42.Kohno T, Mizukami H, Suzuki M, Saga Y, Takei Y, Shimpo M, Matsushita T, Okada T, Hanazono Y, Kume A, Sato I, Ozawa K (2003) Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer. Cancer Res 63:5091–5094Google Scholar
- 49.Furukama S, Soeda S, Kiko Y, Suzuki O, Hashimoto Y, Watanabe T, Nishiyama H, Tasaki K, Hojo H, Abe M, Fujimori K (2013) MCP-1 promotes invasion and adhesion of human ovarian cancer cells. Anticancer Res 33:4785–4790Google Scholar
- 50.Sung WW, Wang YC, Lin PL, Cheng YW, Chen CY, Wu TC, Lee H (2013) IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma. Cancer Res 19:4092–4103Google Scholar
- 54.Rabinovich A, Medina L, Piura B, Huleihel M (2010) Expression of IL-10 in human normal and cancerous ovarian tissues and cells. Eur Cytokine Netw 21:122–128Google Scholar
- 56.Alldredge J, Flies D, Higuchi T, Ma T, Adams SF (2014) Impaired interleukin-10 signaling and ovarian cancer growth in the peritoneal cavity. J Clin Oncol 32(15 suppl):e22094–e22094Google Scholar