Mechano-sensor system of extracelluar matrix to control cancer-associated fibroblast differentiation regulating meningioma progression

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Nagoya University
• Principal Investigator: Tanahashi Kuniaki 名古屋大学, 医学部附属病院, 助教 (90790717)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 髄膜腫 / 間葉系幹細胞 / 癌関連線維芽細胞 / Meflin / Mechanosensor / Hippo pathway

Outline of Final Research Achievements

Meningiomas that arise from skull base regions show poor functional prognosis because they grow along dura mater and involve cranial nerves. They do not have NF2 gene mutations and mechanisms of the growth pattern should be clarified.
Immunohistochemistry of meningiomas from skull base regions showed high expression of Meflin which is reported to be an undifferentiation marker of mesenchymal stem cells. The expression pattern of Hippo pathway-related proteins showed normal NF2 gene function in those meningiomas. Stiffness modulation of extracellular matrix of meningioma cell lines without NF2 mutation implied mechanosensor function for their growth pattern.
The results implied Meningiomas without NF2 mutation has mechanosensor function which is related to mesenchymal stem cells for their growth pattern.

Free Research Field

脳神経外科学関連

Academic Significance and Societal Importance of the Research Achievements

頭蓋底部に発生する髄膜腫は、外科的な摘出が難しいことに加え、硬膜に沿って進展し脳神経を巻き込み障害するために、組織学的に良性であっても機能的予後不良となる。頭蓋底部に発生する髄膜腫は髄膜腫に代表的なNF2遺伝子変異とは異なる遺伝子変異を起源とすることが報告されているが、進展様式との関連は明らかにされていない。本研究により、機能的予後不良の髄膜腫進展様式の解明へ向けた第一歩となることが期待される。