Role of MDSC-mediated premetastatic niche formation in the resistance of Anti-angiogenic agent.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: Mabuchi Seiji 大阪大学, 医学系研究科, 助教 (00452441)
• Research Collaborator: Kawano Mahiru ; Takahashi Ryoko ; Kuroda Hiromasa ; Kozasa Katsumi ; Yokoi Eriko
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 卵巣癌 / 血管新生阻害薬 / 耐性 / Bevacizumab / MDSC / 前転移ニッチ

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.

Free Research Field

婦人科腫瘍学