A functional role of S100A4/non muscle myosin IIA axis for pro‑tumorigenic vascular functions in glioblastoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16201
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kitasato University
• Principal Investigator: Inukai Madoka 北里大学, 医学部, 助教 (10525695)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: Glioblastoma / Hypoxia / Vascular / S100A4 / NMⅡA

Outline of Final Research Achievements

Our results suggest a novel functional role of the S100A4/NMIIA axis in Glioblastoma. Following severe hypoxia, S100A4 is upregulated and interacts with NMIIA; this inhibits NMIIA activity and thus derepresses tumor cell migration. S100A4(+)/HIF-1α(－) tumor cells are subsequently recruited to, and migrate along, preexisting vessels in the presence of extracellular VEGF released by S100A4(+)/HIF-1α(+) Glioblastoma cells. This in turn results in tumor progression through acceleration of vascularization.

Free Research Field

Glioblastoma

Academic Significance and Societal Importance of the Research Achievements

病理組織標本上で可視化した膠芽腫組織内の血管ニッチの分布を応用して、新規予後予測システム等の臨床病理学的因子を構築することができる。S100A4膠芽腫細胞が血管新生のソースであることを明らかにすることによって、血管新生を基軸とした膠芽腫の新たな腫瘍進展機構を提唱できる。S100A4の血管新生などの新たな分子機能を明らかにすることで、様々な悪性腫瘍の発生・進展過程の解析に応用できる。様々な悪性腫瘍のS100A4/NMIIシグナル系による血管新生をターゲットとした治療戦略に応用することができる。