Inappropriate Reprogramming Induce Carcinogenesis of Ovarian Embryonal Carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18169
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yokohama City University
• Principal Investigator: Hayama Tomonari 横浜市立大学, 附属市民総合医療センター, 講師 (70819903)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 卵巣胚細胞性腫瘍 / 発癌 / リプログラミング / モデル動物

Outline of Final Research Achievements

Ovarian embryonic carcinoma (EC) is tumor consisting of phenotypically immature germ cells. The origin of EC was hypothesized as oocytes in ovary. However, the origin and mechanisms of disease onset is still unclear because of no animal model of EC carcinogenesis. As novel EC animal model, we used ovaries of "reprogrammable animal" carrying inducible reprogramming genes. We induced reprogramming of ovaries in vivo, and clarified the origin and molecular mechanism of disease onset. The pre-meiosis oocytes under reprogramming, initially, simple cysts(SC) are formed, among which EC cell mass is formed. Few gene expression changes during reprogramming induce EC cells proliferation, accompanied by differentiated tissues. Those changes are similarly detected in human EC cell line. Our model provides an inducible animal model for carcinogenesis of ovarian EC from ovary. This model will be powerful research tool for mechanism of carcinogenesis, chemical treatment, and early cancer detection.

Free Research Field

産婦人科学

Academic Significance and Societal Importance of the Research Achievements

卵巣胚性癌（EC）はAYA世代に好発する卵巣悪性腫瘍であり、大部分の症例は進行癌で発見され、生命は助かるが妊孕性は失われることが多い。ECの発癌の原因はわかっておらず、早期発見法も確立されていない。我々の開発した発癌動物モデルは、卵巣からECの発癌を誘導する動物モデルを世界で初めて提供した。さらにこのモデルで、卵巣ECの発がんの形態学・分子生物学的機序を解明した。このモデルはECの早期発見方法開発や、化学療法開発などの研究で強力なツールとなることも見込まれる。また本研究は2023年5月に行われた第75回日本産婦人科学会学術総会の婦人科腫瘍部門でJSOG Congress Awardを受賞した。