| Project/Area Number |
16K20202
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Kobayashi Aya 和歌山県立医科大学, 医学部, 博士研究員 (50596971)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | CCR5 / 癌微小環境 / 卵巣癌 / 線維化 / 血管新生 / マクロファージ / 線維芽細胞 / truncated CCL5 vector / 繊維芽細胞 / CCR5発現 / ケモカイン |
|---|
| Outline of Final Research Achievements |
Tumor progression was suppressed in Ccr5-/- mice with intraperitoneal/subcutaneous injections of ID8 cells compared with WT mice.
The chemotactic roles of CCR5 and CCL5 recruit TAMs and CAFs into the tumoral area, leading to the assemblage of tumor microenvironment-favoring cancer cells. Both TAMs and CAFs express CCR5 and supply other growth factors to cancer cells in return, which promotes close communication and interaction between cancer cells and TAMs/CAFs. A (t)RANTES/CCL5 was therapeutically effects on tumor growth by blocking CCR5-mediated signals in this model. As a result, CCR5 signaling in the tumor microenvironment may be responsible for disease progression.
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| Academic Significance and Societal Importance of the Research Achievements |
大腸癌や肺癌などほかの癌腫においてCCR5システムが血管新生や線維化に関与し、癌増殖と関連するとの報告はいくつかあるが卵巣癌を対象にしたものは認めていなかった。今回マウス卵巣癌モデルにおいて宿主CCR5が微小環境における腫瘍血管新生や腫瘍関連線維芽細胞増生に関与し、CCR5の癌進展への関与が明らかとなった。
卵巣癌である程度成果を挙げることができたたため、今後 多くの化学療法抵抗性の固形癌患者の生存率、QOL改善につながる可能性があり、新たな治療戦略の開発に貢献することが期待できる。
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