Elucidation of the mechanism of colorectal cancer-associated fibroblasts to promote cancer malignancy and treatment resistance
| Project/Area Number |
20K09088
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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 55020:Digestive surgery-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
折茂 彰 順天堂大学, 大学院医学研究科, 教授 (70275866)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 大腸癌 / 癌微小環境 / 線維芽細胞 / 浸潤・転移 / オルガノイド / PDXモデル / CAFs / 癌オルガノイド / CAFｓ / 大腸癌線維芽細胞 |
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| Outline of Research at the Start |
大腸癌の間質に多く存在する癌内線維芽細胞 (Carcinoma-associated fibroblasts : CAFs)は癌細胞の浸潤、転移や治療抵抗性獲得に関与していることが知られているが、その分子機構はまだ不明な点が多い。本研究では、大腸癌由来CAFsを抽出し、ヒト大腸癌の浸潤、転移や治療抵抗性獲得に与える影響を解明する。CAFsとヒト大腸癌細胞の相互作用を媒介する遺伝子やシグナルの同定し、大腸癌悪性化や治療抵抗性獲得を抑制する新規根治療法の基礎を前臨床マウスモデルを用いて確立することを目標とする。
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| Outline of Final Research Achievements |
We collected specimens from colon cancerous and non-cancerous areas resected by surgery, and successfully established 21 cases of CAFs and control fibroblasts. We also established 8 colon cancer organoids. Immunohistochemical staining using a cell-specific antibody 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. In the future, we will establish a 3D colon cancer organoid culture, establish a co-culture system of CAFs and colon cancer organoids, prepare a PDX model by orthotopic co-transplantation into mice, and conduct biological research on cancer invasion and metastasis induced by CAFs.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性大腸癌の転移再発に対する現行の抗癌剤の治療効果は不十分であり、根治的治療の開発が望まれている。大腸癌の間質に多く存在する線維芽細胞は癌浸潤、転移や治療抵抗性獲得に関与していることが知られているが、その分子機構の理解は不十分である。本研究は、大腸癌由来線維芽細胞を抽出し、大腸癌の浸潤、転移や治療抵抗性獲得に与える影響を分子レベルで解明することにより癌悪性化機構の理解を深める意義がある。
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Report
(4 results)
Research Products
(2 results)
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[Journal Article] Pyoderma gangrenosum in an ulcerative colitis patient during treatment with vedolizumab responded favorably to adsorptive granulocyte and monocyte apheresis2020
Author(s)
Tomoyoshi Shibuya 1, Keiichi Haga 1, Michio Saeki 1, Mayuko Haraikawa 1, Hitoshi Tsuchihashi 2, Koki Okahara 1, Osamu Nomura 1, Hirofumi Fukushima 1, Takashi Murakami 1, Dai Ishikawa 1, Shigaku Ikeda 2, Akihito Nagahara 1
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Journal Title
J Clin Apher .
Volume: 35
Issue: 5
Pages: 488-492
DOI
Related Report
Peer Reviewed
