Functional analysis of cancer-associated mesothelial cells aimed at disease control of advanced ovarian cancer and development of peritoneal restoration therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16788
• 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: Nagoya University
• Principal Investigator: Yoshihara Masato 名古屋大学, 医学部附属病院, 病院助教 (00878374)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 卵巣癌 / 腹膜播種 / 中皮細胞

Outline of Final Research Achievements

Effective treatments for advanced ovarian cancer with peritoneal dissemination have yet to be established, and new therapeutic strategies to overcome this intractable disease are highly anticipated. We have previously identified ovarian cancer-associated peritoneal mesothelial cells (OCAM) within the peritoneal microenvironment of advanced ovarian cancer. In this study, we elucidated the molecular biological mechanisms by which normal peritoneal mesothelial cells, which originally have a "protective" function, convert into "cancer allies" that promote the progression of ovarian cancer. This was achieved through lineage tracing of peritoneal mesothelial cells using genetically modified animal models. Furthermore, targeting the process by which normal peritoneal mesothelial cells transform into OCAM, we explored unknown candidate substances that could inhibit this change using a chemical library.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

WT-1遺伝子の下流にCreERT2を発現させ、loxP領域にtdTomatoを挿入したコンディショナルノックインマウスに対して卵巣癌腹膜播種を形成し、OCAMへの変化の過程を詳細に観察し、さらに血管関連細胞への偏分化を示した。動物実験を主体としたこれまでの成果をまとめ、論文投稿を行なっている。さらに正常腹膜中皮細胞がOCAMへと変貌する過程を標的としたスクリーニングシステムの樹立に取り掛かり、知財申請を完了した。ケミカルライブラリースクリーニングを実施したところ、中皮細胞の間葉転換を抑制する10個の候補物質を同定した。本研究成果を基盤として、中皮細胞標的治療の確立を目指して行く。