Base construction for the development of therapeutic strategies for targeting the invasiveness in malignant glioma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kagoshima University
• Principal Investigator: IIJIMA Mikio 鹿児島大学, 医歯学域医学系, 助教 (00305111)
• Co-Investigator(Kenkyū-buntansha): 岸田 昭世 鹿児島大学, 医歯学域医学系, 教授 (50274064)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: グリオーマ / 浸潤性 / 受容体 / MMP-2

Outline of Final Research Achievements

Glioma and ameloblastoma is characterized by marked invasiveness, but little is known about the mechanism of invasion in glioma cells and ameloblastoma cells. Controlling the degradation of extracellular matrix by proteases could be a candidate for novel glioma and ameloblastoma management. Up-regulation of MMP-2 has been reported and suggested to deteriorate tumor invasiveness in glioma. Ryk is important for the Wnt-5a-dependent induction of MMP-2 and invasive activity in glioma-derived cells. To construction for the development of therapeutic strategies for targeting the invasiveness in malignant glioma, we identified RYK-associated proteins by using yeast two-hybrid system and fragmented length cDNA libraries. In ameloblastoma cells, IL-1 is a key mediator to control its microenvironment and local invasion. Osteoblast-derived factors induced the production of MMP-2 by ameloblastoma cells.

Free Research Field

シグナル伝達

Academic Significance and Societal Importance of the Research Achievements

高い浸潤能を特徴とするグリオーマやエナメル上皮種において、その浸潤能を制御できれば、病態の制御が容易になると考えられる。グリオーマ細胞でのWnt-5aによるRyk受容体を介したMMP-2発現上昇とエナメル上皮腫由来IL-1刺激による骨芽細胞由来の因子を介したMMP-2発現上昇が示された。これらのシグナル経路の詳細が明らかになれば、学術的意義のみならず、治療のための新たなターゲットが得られるという罹患者にとっての意義が提供できると思われる。