Role of MDSC-mediated premetastatic niche formation in the resistance of Anti-angiogenic agent.
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 |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Osaka University |
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)
|
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 |
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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Report
(4 results)
Research Products
(18 results)
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[Journal Article] The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer.2015
Author(s)
Kawano M, Mabuchi S, Matsumoto Y, Sasano T, Takahashi R, Kuroda H, Kozasa K, Hashimoto K, Isobe A, Sawada K, Hamasaki T, Morii E, Kimura T.
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Journal Title
Scientific Reports
Volume: 15;5
Issue: 1
Pages: 18217-18217
DOI
Related Report
Peer Reviewed / Open Access
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