Tumor-specific CD73-induced hypoxia-responsive growth mechanism in the extracellular matrix environment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10109
• 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: Niigata University
• Principal Investigator: Maruyama Satoshi 新潟大学, 医歯学総合病院, 講師 (30397161)
• Co-Investigator(Kenkyū-buntansha): 阿部 達也 新潟大学, 医歯学系, 助教 (70634856) ; 山崎 学 新潟大学, 医歯学系, 准教授 (10547516) ; 田沼 順一 新潟大学, 医歯学系, 教授 (20305139)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Hypoxia / HIF-1α / CD73 / Pleomorphic adenoma

Outline of Final Research Achievements

In this study, we investigated the role of CD73, one of the target molecules of the hypoxia-inducible factor (HIF) activation mechanism, in cell function under hypoxia was investigated. Cell function analysis using the SM-AP cell line, a salivary gland pleomorphic adenoma-derived cell line, indicated that tumor cells themselves may express CD73 in the tumor stroma, where extracellular matrix is abundant, to enhance tumor cell proliferation and migration ability, and to survive and maintain the cells. Comprehensive analysis of cell proliferation-related humoral factors revealed several candidate molecules, such as CXCL10, that could be considered as candidate molecules for CD73-mediated hypoxia-responsive growth mechanisms. Histological analysis of human tumor tissue material suggested the possibility of CD73 supply from stromal cells instead of tumor cells in tumors with stromal induction such as lymphocytes and fibrosis in addition to tumor cells.

Free Research Field

口腔病理学

Academic Significance and Societal Importance of the Research Achievements

腫瘍は低酸素状態という特異な微小環境下において、低酸素誘導因子(Hypoxia inducible factors: HIF)により引き起こされる低酸素応答を介した生存・増殖をおこなっている。今回、我々はHIF活性化機構の標的分子の一つであるCD73が低酸素下で細胞機能に果たす役割を検討した。その結果、細胞外基質が豊富な腫瘍間質の中で、HIF活性化機構の標的分子の一つであるCD73の高発現が、腫瘍細胞の増殖や遊走能を亢進し、生存・維持に寄与している可能性が示された。CD73を介した腫瘍特異的な低酸素応答性増殖機構を標的とした新たな抗腫瘍治療への展望を見出すことができたと考える。