Elucidating the mechanisms of intracellular communication within the peritoneal cavity inducing the construction of a dormancy-maintaining environment for occult cancer metastasis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19562
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Nagoya University
• Principal Investigator: Kajiyama Hiroaki 名古屋大学, 医学系研究科, 教授 (00345886)
• Co-Investigator(Kenkyū-buntansha): 吉原 雅人 名古屋大学, 医学部附属病院, 病院助教 (00878374) ; 横井 暁 名古屋大学, 医学部附属病院, 病院講師 (30737135) ; 芳川 修久 名古屋大学, 医学部附属病院, 講師 (60804747)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 卵巣癌 / 腹膜播種 / 休眠 / 細胞間コミュニケーション

Outline of Final Research Achievements

Cancer patients with peritoneal dissemination often experience recurrence after a period of "dormancy," even if they achieve remission through treatment. Various cytotoxic antitumor drugs and molecular targets have been used as maintenance therapy, but unfortunately, none can completely eradicate the "dormant cancer cell clusters (seeds)." This study aims to elucidate, through interdisciplinary research, the mechanisms by which cancer-associated mesothelial cells (CAM) assist in the dormancy and evolution of tumor cells and help them evade attacks from existing antitumor drugs. By exploring the maintenance mechanisms of intra-abdominal occult seeding by CAM, we attempted to develop a comprehensive treatment strategy targeting the entire peritoneum and identify novel biomarkers.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

OCAMに発現するNotchリガンドの一つであるDLL3を介して、一部の卵巣癌細胞にNotchシグナルが誘導され、Notch陽性となった卵巣癌細胞は、幹細胞形質を獲得し、細胞周期の遅延や低栄養耐性などの休眠様の状態を呈することを解明した。Notch陽性細胞はアミノ酸の代謝変容を引き起こし、プラチナ製剤などへのストレス抵抗性を獲得している機序を明らかにし、この機序を標的とした薬剤候補を同定し、その効果を各種実験モデルで実証した。本研究成果を基盤として、OCAMを標的とした新規治療戦略の確立を目指して行く。