2022 Fiscal Year Final Research Report
Role of fibroblasts in the colorectal cancer metastasis niche
| Project/Area Number |
20K17664
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 大腸癌 / 癌微小環境 / 転移 / オルガノノイド |
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| Outline of Final Research Achievements |
In this study, in order to clarify the role of CAFs in the metastatic niche of colorectal cancer, we isolated CAFs and control fibroblasts after enzymatic treatment of specimens collected from human colorectal cancer and non-cancer areas in 21 colon cancer patients. We also established 8 colon cancer organoids by enzymatically treating a part of the cancer tissue. Immunohistochemical staining confirmed the establishment of highly pure fibroblasts. In addition, RNA-sequencing identified multiple genes that were significantly upregulated in CAFs compared to non-cancerous control fibroblasts. We have thus successfully established fibroblasts and human colon cancer organoids from clinical samples required for research.
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| Free Research Field |
癌生物学
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| Academic Significance and Societal Importance of the Research Achievements |
癌死亡の90％は転移に起因しているが、転移のメカニズムは未だ明らかでない。大腸癌細胞が遠隔臓器に転移した後、癌細胞の増殖を促進するための微小環境（ニッチ）が形成されることが知られている。しかしながら、転移ニッチは血管構成細胞や炎症免疫細胞などの様々な非癌細胞より構成されており、癌細胞増殖に重要な遺伝子やシグナルの同定は不十分である。本研究では患者大腸癌よりCAFsや癌オルガノイドを樹立しヒト大腸癌モデルを作製し、転移巣で形成されたニッチでの細胞―細胞相互作用や分子メカニズム調査することにより転移の機序を解明することが可能である。
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