Malignant ascites enhances migratory and invasive properties of ovarian cancer cells with membrane bound IL-6R in vitro
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Soochi Kim1,2, HyeRan Gwak2,3, Hee Seung Kim2,4, Boyun Kim2,5, Danny N. Dhanasekaran6, Yong Sang Song1,2,3,4
1Interdisciplinary Program in Cancer Biology, College of Medicine, Seoul National University, Seoul, Republic of Korea
2Cancer Research Institute, Seoul National University, Seoul, Republic of Korea
3Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
4Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea
5Nano System Institute, Seoul National University, Seoul, Korea
6Stephenson Cancer Center, University of Oklahoma Health Sciences Center, USA
Yong Sang Song, email: [email protected]
Keywords: ascites, migration, invasion, IL-6R, ovarian cancer
Received: April 18, 2016 Accepted: October 11, 2016 Published: November 4, 2016
Transcoelomic route is the most common and the earliest route of metastasis, causing the ascites formation in advanced epithelial ovarian cancer (EOC). We demonstrated that interleukin 6 (IL-6) is enriched in the malignant ascites from patients with ovarian cancer, which enhanced invasive properties of EOC cells. Interestingly, the expression of IL-6R on cell membrane of EOC cells correlated with ascites-induced invasion. Selective knockdown of IL-6R or inhibition with IL-6 neutralizing antibody, suppressed the stimulatory effects of ascites on EOC invasion. Moreover, the ascites treatment induced the phosphorylation of JAK2-STAT3 and use of selective inhibitors of JAK2 and STAT3, blocked the expression of epithelial-mesenchymal transition related proteins in parallel with the suppression of EOC invasion. Thus, IL-6/IL-6R mediated JAK2-STAT3 signaling pathway could be a promising therapeutic target for anticancer therapy in ovarian cancer patients with ascites.
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