2020 Fiscal Year Final Research Report

Novel strategy targeting myeloid cells-mediated invasion of oral cancer

Research Project

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Project/Area Number	18K09741
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57060:Surgical dentistry-related
Research Institution	University of Toyama
Principal Investigator	Noguchi Makoto 富山大学, 学術研究部医学系, 教授 (50208328)
Co-Investigator(Kenkyū-buntansha)	山崎学新潟大学, 医歯学系, 助教 (10547516) 笹原正清富山大学, 学術研究部医学系, 教授 (20154015) 藤原久美子富山大学, 学術研究部医学系, 助教 (60404737) 冨原圭富山大学, 学術研究部医学系, 准教授 (70404738)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	口腔癌 / 局所浸潤過程 / 癌関連線維芽細胞 / 破骨細胞分化 / 免疫抑制性細胞
Outline of Final Research Achievements	In this study, we aimed to establish novel strategy to target myeloid derived suppressor cell (MDSC)-mediated invasion of oral cancer. Osteoclast differentiation is crucial for bone invasion of oral cancer and one of the cell surface marker for osteoclast is CD11b which is also the marker of MDSC. Therefore, the similarity of osteoclast and MDSC have been suggested. Moreover, the cancer-associated fibroblasts are also important for tumor invasion in various cell types of cancer. We observed that PDGFR-alpha positive cells were accumulated in oral cancer-bearing mice and these cells also expressed CD11b and Gr-1, suggesting that association between CAF and MDSC. Moreover, we purified these CD11b+, Gr-1+ cells from spleen, peripheral blood, and tumor tissue, and evaluated the capacity for osteoclast differentiation. CD11b+, Gr-1+ cells from tumor tissue exhibited significantly increased capacity for osteoclast differentiation compared to those from other sites.
Free Research Field	口腔外科学
Academic Significance and Societal Importance of the Research Achievements	口腔扁平上皮癌の顎骨浸潤を誘導する破骨細胞も、MDSC同様にCD11b陽性の骨髄系由来の細胞である。また、腫瘍の浸潤には、腫瘍組織内の線維芽細胞である、いわゆる癌関連線維芽細胞cancer associated fibroblast（以下CAF）が重要な役割を果たすことも示唆されている。腫瘍浸潤過程におけるMDSCの果たす役割を解明することを目的とした本研究は、極めて新規性の高い研究と考えられる。以上、本研究により、口腔扁平上皮癌の浸潤局所における免疫応答からみたCAF発生、破骨細胞分化機序の一端が解明されれば、これを標的とした標的化治療の開発に繋がることが期待される。