Malignant ascites enhances migratory and invasive properties of ovarian cancer cells with membrane bound IL-6R in vitro.
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.
Interdisciplinary Program in Cancer Biology, College of Medicine, Seoul National University, Seoul, Republic of Korea.|Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
Soochi
S
Kim
Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.|Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
HyeRan
H
Gwak
Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.|Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea.
Hee Seung
HS
Kim
Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.|Nano System Institute, Seoul National University, Seoul, Korea.
Boyun
B
Kim
Stephenson Cancer Center, University of Oklahoma Health Sciences Center, USA.
Danny N
DN
Dhanasekaran
Interdisciplinary Program in Cancer Biology, College of Medicine, Seoul National University, Seoul, Republic of Korea.|Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.|Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Department of Obstetrics and Gynecology, Seoul National University, Seoul, Republic of Korea.
Yong Sang
YS
Song
D000368:Aged; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001201:Ascites; D001202:Ascitic Fluid / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
IL-6R; ascites; invasion; migration; ovarian cancer