The development of a novel microRNA replacement therapy for ovarian cancer - a potential of patient derived-exosomes as a carrier.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Sawada Kenjiro 大阪大学, 医学系研究科, 講師 (00452392)
• Co-Investigator(Kenkyū-buntansha): 馬淵 誠士 奈良県立医科大学, 医学部, 講師 (00452441) ; 小玉 美智子 大阪大学, 医学系研究科, 助教 (70791391) ; 木村 正 大阪大学, 医学系研究科, 教授 (90240845) ; 橋本 香映 大阪大学, 医学部附属病院, 特任准教授(常勤) (90612078)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 卵巣癌 / マイクロRNA / エクソソーム / バイオマーカー / DDS / 腹膜播種

Outline of Final Research Achievements

MicroRNAs (miRNAs) affect key features of cancer cells. Exosomes are stable in body fluid and therefore can serve as a promising candidate for miRNA carrier. In ovarian cancer treatment, omentum should be taken at surgery and normal fibroblasts can be collected from omentum. The aim of this study is to pursue the possibility of fibroblast derived-exosomes as a carrier for miRNA replacement therapy. At surgery, omentum was collected and fibroblasts were primary cultured. Thereafter, exosomes were collected from culture media. Synthesized miR-199a-3p was corporated into exosomes by electroporation. The treatment of miR-199a-3p-loaded exosomes (M199-exosomes) was assessed. The treatment of M199-exosomes drastically increased miR-199a-3p expression followed by c-Met down-regulation and significantly inhibited the proliferation and invasion of ovarian cancer cells in vitro and in vivo. As a conclusion, exosomes derived from patients’ fibroblasts can serve as superior carrier of miRNA.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

卵巣癌患者大網由来のエクソソームを核酸試薬のキャリアとして用いた場合、卵巣がん細胞への選択性と効率の高い核酸の取り込みが期待でき、治療効果が期待できることを証明した。今後の新規の核酸治療への応用の可能性を提示した。腹膜播種は腹膜癌や婦人科癌に留まらず、胃癌や大腸癌などの消化器癌においても、極めて難治で、治癒はほぼ不可能である。今回の研究成果は、消化器癌などにおける腹膜播種形成にも応用できると考えており、新規の癌治療として臨床応用できる可能性を有している。