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

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 髄膜腫 / 間葉系幹細胞 / 癌関連線維芽細胞 / Meflin / Mechanosensor / Hippo pathway / YAP / 細胞外基質硬度 / 間葉系幹細胞(MSC) / 癌関連線維芽細胞(CAF) / Mechano-sensor

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.

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。

Research Products

• [Journal Article] Trautmann-focused mastoidectomy for a simple, safe presigmoid approach: technical note. (2020)
  • Author(s): Tanahashi K, Uda K, Araki Y, Takeuchi K, Choo J, Chalise L, Motomura K, Ohka F, Wakabayashi T, Natsume A.
  • Journal Title: J Neurosurg. Volume: 3 Issue: 3 Pages: 1-5
  • DOI: 10.3171/2020.1.jns193179
  • Peer Reviewed
• [Presentation] Usefulness of simple presigmoid exposure for cerebellopontine angle and brain stem lesions (2019)
  • Author(s): Tanahashi K, Takeuchi K, Uda K, Chalise L, Motomura K, Natsume A, Wakabayashi T
  • Organizer: 2019 WFNS SPECIAL WORLD CONGRESS
• [Presentation] 最小錐体骨削除によるpresigmoid approach (2019)
  • Author(s): 棚橋邦明、竹内和人、宇田憲司、本村和也、夏目敦至、若林俊彦
  • Organizer: 日本脳神経外科学会第78回学術総会
• [Presentation] 鞍結節部髄膜腫に対する開頭術と経鼻内視鏡手術の術後成績の検討 (2019)
  • Author(s): 棚橋邦明、竹内和人、本村和也、夏目敦至、若林俊彦
  • Organizer: 第37回日本脳腫瘍学会学術集会