Why is the treatment of peritoneal dissemination so difficult? Analyses focusing on microRNA and exosome.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293360
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: Sawada Kenjiro 大阪大学, 医学(系)研究科(研究院), 講師 (00452392)
• Co-Investigator(Kenkyū-buntansha): 馬淵 誠士 大阪大学, 医学(系)研究科(研究院), 助教 (00452441) ; 木村 正 大阪大学, 医学(系)研究科(研究院), 教授 (90240845) ; 橋本 香映 大阪大学, 医学(系)研究科(研究院), 助教 (90612078) ; 磯部 晶 大阪大学, 医学(系)研究科(研究院), 助教 (60397619)
• Research Collaborator: Kinose Yasuto ; Nakamura Koji ; Yoshimura Akihiko
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Ovarian cancer / peritoneal dissemination / microRNA / exosome / paclitaxel

Outline of Final Research Achievements

The overcome of paclitaxel resistance is a critical issue in ovarian cancer treatment. We aimed to identify key miRNAs which regulate paclitaxel resistance and to pursue those potential as therapeutic targets. Two paclitaxel resistant ovarian cancer cell lines were established by a continuous exposure. MiRNA PCR arrays were performed and miR-194 was found to be one of down-regulated miRNAs. We found that miR-194 acts as a tumor suppressor miRNA through the sensitization to paclitaxel and can be considered as a therapeutic target for paclitaxel-resistant ovarian cancer. Further, we aimed to identify the functional roles of ovarian cancer-derived exosomes during peritoneal dissemination. Exosomes were isolated from ovarian cancer cell lines. Ovarian cancer invasion was significantly promoted in the presence of exosome-treated human peritoneal mesothelial cells (HPMCs). We proved that ovarian cancer-derived exosomes transfer CD-44 to HPMCs, which can facilitate ovarian cancer invasion.

Free Research Field

婦人科腫瘍学