Construction of therapeutic methods targeting ADAM9 expressed in cancer-related fibroblasts and search for new target molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Defense Medical College
• Principal Investigator: Mochizuki Satsuki 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 外科学, 講師 (80365428)
• Co-Investigator(Kenkyū-buntansha): 上野 秀樹 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 外科学, 教授 (90597535)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ADAM / ECM / 癌微小環境 / 癌関連線維芽細胞 / 線維性癌間質反応

Outline of Final Research Achievements

Desmoplastic reaction (DR), which is morphologically classified to Mature, Intermediate and Immature types, is correlated with patient prognosis. Conditioned media of CAFs from tumor with Immature type DR (CAFsImmature) significantly increased proliferation and migration of CRC cells compared to those of CAFs from Mature-type DR (CAFsMature). Subcutaneous implantation of CRC cells together with CAFsImmature in mice significantly promoted tumor growth and peritoneal dissemination compared to those with CAFsMature. Systematic examination indicated that ADAM9s expression is significantly higher in CAFsImmature than in CAFsMature. Knockdown of ADAM9s in CAFsImmature suppressed the promoting effects on CRC cell proliferation and migration. ADAM9s overproduced by CAFsImmature has been suggested to promote CRC cell proliferation and migration, suggesting an impact on poor prognosis of patients with Immature-type DR.

Free Research Field

癌微小環境

Academic Significance and Societal Importance of the Research Achievements

本研究による研究成果は、「 Cancer-associated fibroblasts at the unfavorable desmoplastic stroma promote colorectal cancer aggressiveness」のタイトルでInt J Cancer 15: 1706-1721, 2022 誌に責任著者として発表し、本論文は2022年度日本結合組織学会大高賞を受賞した。