Oncotarget

Research Papers:

Malignant ascites enhances migratory and invasive properties of ovarian cancer cells with membrane bound IL-6R in vitro

Soochi Kim _, HyeRan Gwak, Hee Seung Kim, Boyun Kim, Danny N. Dhanasekaran and Yong Sang Song

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Oncotarget. 2016; 7:83148-83159. https://doi.org/10.18632/oncotarget.13074

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Abstract

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

Correspondence to:

Yong Sang Song, email: yssong@snu.ac.kr

Keywords: ascites, migration, invasion, IL-6R, ovarian cancer

Received: April 18, 2016    Accepted: October 11, 2016    Published: November 4, 2016

ABSTRACT

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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