Elucidation of the mechanism of vasohibin-2 for cancer progression
| Project/Area Number |
16H04689
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Tohoku University |
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Principal Investigator |
Sato Yasufumi 東北大学, 加齢医学研究所, 教授 (50178779)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 康弘 東北大学, 加齢医学研究所, 助教 (60332277)
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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 |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | VASH2 / 膵がん / 転移 / αチューブリン脱チロシン化 / 骨髄由来免疫抑制細胞 / M2マクロファージ / がん免疫 / 血管新生 / M2マクローファージ / Vasohibin-2 / がん転移 / 脱チロシン化チューブリン / Vash2 / KPCマウス / 浸潤 / 上皮間葉転換 / がん随伴線維芽細胞 / TGF-β / TGFβ I型受容体 / 癌 |
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| Outline of Final Research Achievements |
We first examined the role of VASH2 in ovarian cancer cells. Our analyses revealed that VASH2 was involved in the expression of TGF-β type I receptor, which influenced the TGF-β-mediated epithelial-mesenchymal transition for cancer cell invasion. We then examined the role of VASH2 in pancreatic cancer by using KPC mice and cells isolated from them. Knockdown of Vash2 significantly decreased migration of KPC cells. When KPC mice were crossed with Vash2 deficient mice, metastasis was significantly decreased. Our analyses revealed that Vash2 increased tubulin detyrosination of KPC cells for their migration and invasion. We further revealed that Vash2 was involved in the expression of CXCR2 ligands and G-CSF, which were responsible for the recruitment of myeloid derived suppressor cells (MDSCs) and M2-macrophages for the evasion of tumor immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、実施者が発見したVASH2が、がんの進展の中で、特にその転移において極めて重要な役割を果たしていることが明らかとなった。我が国の死亡原因のトップであり、なかでも最も悪性で難治性の膵がんは、早期の外科療法以外に確実な治療法のない状況は続いている。本研究成果は、こうした膵がんをはじめとした難治がんに対する新しい治療法をもたらすものである。
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Report
(4 results)
Research Products
(4 results)
