Growth patterns of meningiomas based on their locations and embryologic backgrounds of the meninges, and the role of the mesenchymal stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17928
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• 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): 2020-04-01 – 2023-03-31
• Keywords: 髄膜腫 / 間葉系幹細胞 / 癌関連線維芽細胞 / Meflin / 足場硬度 / 細胞外基質 / オルガノイド

Outline of Final Research Achievements

Meningiomas on skull base regions, which do not derive from NF2 mutations in contrast to those on brain surfaces, show poor functional prognosis because they grow along the dura mater and involve the cranial nerves. The mechanism of the growth pattern should be clarified. An analysis of profiling data of meningiomas showed tendency of lower expression of Meflin, a maker protein of undifferentiation of the mesenchymal stem cells (MSCs), in skull base meningiomas. Combined with the findings that differentiation of MSCs into cancer-associated fibroblasts is associated with scaffold stiffness, and that increased extracellular matrix stiffness activates meningioma cell lines without NF2 gene mutations, relationship between skull base meningioma growth patterns and MSC differentiation was suggested. In addition, using meningioma tissues, from which it is supposed to be difficult to establish cell lines, we established a new organoid culture method and succeeded in culturing multiple strains.

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。頭蓋底部髄膜腫は脳表部に発生する髄膜腫に多くみられるNF2遺伝子変異とは異なる遺伝子変異が起源とされるが、その進展機序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。