Identification of biomarkers for tumor-promoting CAFs
| Project/Area Number |
18K07207
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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 50010:Tumor biology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Orimo Akira 順天堂大学, 医学(系)研究科(研究院), 教授 (70275866)
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| Co-Investigator(Kenkyū-buntansha) |
ワリ ナディラ 順天堂大学, 医学(系)研究科(研究院), 非常勤助教 (90751868)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | CAFs / TGF-b / Endoglin / 癌促進 / 乳癌 / 癌浸潤・転移 / CAFｓ / TGF-bシグナル / 癌微小環境 / endogln / TGF-ｂシグナル / 癌内線維芽細胞 / endoglin (CD105) |
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| Outline of Final Research Achievements |
Applicants found that cancer-associated fibroblasts (CAFs), which are abundant in the cancer microenvironment, act on nearby breast cancer cells to promote cancer malignant transformation. It has been shown that activation of stromal cell-derived factor 1 (SDF-1) and TGF-β autocrine signal is important for maintaining the phenotype of cancer-promoting CAFs. In addition, the applicants recently found that TGF-β receptor-binding protein endoglin (CD105) is highly expressed in breast cancer-derived CAFs by DNA microarray analysis. In this study, it was clarified that endoglin, which is the co-receptor of TGF-β, is highly expressed on CAFs, activates the TGF-β-Smad2/3 signal, and maintains myofibroblastic and cancer-promoting abilities. Furthermore, it was clarified that the expression of endoglin in CAFs is useful as a biomarker for predicting the prognosis of CAFs.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らは、独自に樹立した乳癌由来CAFsを使用し、対照的に非癌部より抽出された線維芽細胞との比較により、CAFsで遺伝子発現が変化している独自の遺伝子群を同定し、本研究では、endoglinに焦点を当て、CAFsでTGF-bやSDF-1オートクラインシグナルとの関与を明らかにした。また、本研究ではCAFsにおけるendoglinの発現が、患者の予後予測マーカ―になることを明確にした。さらに、CAFsにおけるendoglinの発現抑制を基に、CAFsを標的にした新規癌治療法の開発に今後役立つ可能性を見出した。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state.2020
Author(s)
Mizukoshi K, Okazawa Y, Haeno H, Koyama Y, Sulidan K, Komiyama H, Saeki H, Ohtsuji N, Ito Y, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
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Journal Title
Int J Cancer .
Volume: 146
Pages: 2547-2562
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-sensitivity detection of micrometastases generated by GFP lentivirus-transduced organoids cultured from a patient-derived colon tumor.2019
Author(s)
OkazawaY, Mizukoshi K, KoyamaY, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
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Journal Title
J. Vis. Exp.
Volume: 136(e57374)
Pages: 136-136
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling.2019
Author(s)
Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, Lehn S, Sjölund J, Reid S, Larsson C, Eriksson P, Anderberg C, Cortez E, Saal LH, Orsmark-Pietras C, Cordero E, Haller BK, Häkkinen J, Burvenich IJG, Lim E, Orimo A, Höglund M, Rydén L, Moch H, Scott AM, Eriksson U, Pietras K.
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Journal Title
Nat. Med
Volume: 24(4)
Pages: 463-467
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Activation of Src signaling mediates carcinoma-associated fibroblast-promoted metastasis in human breast cancers.2018
Author(s)
Yasuhiko Ito, Yuko Matsumura, Yoshihiro Mezawa, Kaidiliavi Sulidan, Nadila Wali, Yasuhisa Terao, Satoru Takeda, Ko Okumura, Kazuyoshi Takeda, Okio Hino, Akira Orimo
Organizer
第77回日本癌学会学術総会 大阪
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