2021 Fiscal Year Final Research Report
Mechanisms of colon cancer development by Interleukin-11-producing cancer-associated stromal cells
| Project/Area Number |
19K07391
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Toho University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 大腸がん / 間質細胞 / 線維芽細胞 / Interleukin-11 / 炎症 / Apcmin / オルガノイド / 大腸炎 |
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| Outline of Final Research Achievements |
Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.
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| Free Research Field |
病態生化学
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| Academic Significance and Societal Importance of the Research Achievements |
大腸がんの発生や進展において、がん細胞の周囲に存在する細胞の重要性が示唆されているが、その詳細な分子機構に関しては未だ不明な点が多い。本研究においては、大腸がん増悪に働くIL-11が、がん細胞ではなく、その周囲に存在する間質細胞で特異的に産生されていることを見出した。さらに、得られた知見はヒト大腸がん検体とも強い相関が認められた。すなわち、本研究は大腸がん形成において重要な働きを示す繊維芽細胞においてIL-11は新たな細胞マーカーとしての役割を提示するものであり、IL-11産生がん関連間質細胞の特性を明らかにすることは、今後大腸がんの新たな治療標的を見出すうえで重要になると考えられる。
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