| Project/Area Number |
26462523
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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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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
Mabuchi Seiji 大阪大学, 医学系研究科, 助教 (00452441)
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| Co-Investigator(Kenkyū-buntansha) |
澤田 健二郎 大阪大学, 医学系研究科, 講師 (00452392)
橋本 香映 大阪大学, 医学系研究科, 助教 (90612078)
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| Research Collaborator |
Kawano Mahiru
Takahashi Ryoko
Kuroda Hiromasa
Kozasa Katsumi
Yokoi Eriko
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 卵巣癌 / 血管新生阻害薬 / 耐性 / Bevacizumab / MDSC / 前転移ニッチ / Bevacizumab耐性化 / 転移・浸潤 / 耐性化 |
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| Outline of Final Research Achievements |
MDSC was observed in the peripheral blood of tumor-bearing mice treated with bevacizumb. MDSC expressed Bv8 and significantly enhanced the angiogenesis. MDSC-inhibition significantly enhanced the anti-tumor effect of bevacizumab. In the premetastatic lungs of tumor-bearing mice, markedly increased MDSC cells were observed. MDSC in the premetastatic lungs expressed S100a8, S100a9, and MMP9. Moreover, MDSC expressed Cxcl2 to attract cancer cells that express CXCR2. MDSC-inhibition using anti-Gr-1 inhibited the expression of Cxcl2, S100a8, S100a9, Mmp9 and Bv8, and significantly reduced the pulmonary metastases. These results indicate that MDSC contribute to the formation of a premetastatic niche by generating an immunosuppressive, inflammatory, and pro-angiogenic environment which can facilitate tumor cell metastasis.
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