Dissecting molecular mechanisms underlying formation of tumor-promoting niches by colon cancer cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Juntendo University
• Principal Investigator: sakamoto naoto 順天堂大学, 医学部, 客員准教授 (10420845)
• Co-Investigator(Kenkyū-buntansha): 折茂 彰 順天堂大学, 医学(系)研究科(研究院), 教授 (70275866)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: CAFs / 大腸癌 / 癌organoid / PDXs

Outline of Final Research Achievements

Applicants found that cancer cell lines induce TGF-b signals in normal fibroblasts and promote their differentiation into fibroblasts (CAFs), the representative stromal cells of the cancer-promoting niche. However, the factors derived from cancer cells that contributed to the formation of the CAFs niche and the characteristics of the cancer cells themselves are not clear. In the submitted study, multiple colorectal cancer patient-derived tumor xenograft (PDX) and cancer organoids were established without using a specific cancer cell line, and their ability to induce cancer-promoting CAFs was compared and examined to compare cancers. We attempted to elucidate the interaction between cells and CAFs at the molecular level.

Free Research Field

癌生物学

Academic Significance and Societal Importance of the Research Achievements

癌塊内にCAFsが豊富に存在すると予後不良であることが疫学的調査により報告されている。しかしながら、癌細胞の悪性度とCAFsを癌塊内にリクルートしニッチを形成する能力の相関に関して、細胞および実験動物レベルでの研究報告は乏しい。申請研究の独創性はCAFsニッチを形成する能力が癌悪性化の１つの指標であることを大腸癌PDXsや癌organoidを使用し分子レベルで明らかにすることである。