Growth patterns of meningiomas based on their locations and embryologic backgrounds of the meninges, and the role of the mesenchymal stem cells
| Project/Area Number |
20K17928
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| 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 / YAP / Mechano-sensor / Hippo pathway |
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| Outline of Research at the Start |
脳腫瘍の多くを占める髄膜腫の中には、脳底部に広がるように増大するものがあり、脳神経を巻き込んで障害するため外科的治療が難しい。髄膜腫がこのように増大する機序は未だ解明されていない。
本研究では、髄膜腫が発生部位ごとに特徴的な遺伝子変異をもつことと、脳底部の正常髄膜が形作られる由来組織（中胚葉）に着目し、髄膜腫増大のメカニズムを解明することを目的とする。脳底部における髄膜組織に特徴的な幹細胞が、髄膜腫発育の足場環境を作り出しているという仮説を立て、髄膜腫摘出検体・培養髄膜腫細胞・髄膜腫マウスモデルを用いて解析することで、これを明らかにする。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] 11C-methionine- and 18F-FDG-PET double-negative metastatic brain tumor from lung adenocarcinoma with paradoxical high 18F-FDG uptake: A case report2022
Author(s)
Kuniaki Tanahashi, Masaki Hirano, Lushun Chalise, Takahiko Tsugawa, Yuka Okumura, Tetsunari Hase, Fumiharu Ohka, Kazuya Motomura, Kazuhito Takeuchi, Yuichi Nagata, Norimoto Nakahara, Naozumi Hashimoto, Ryuta Saito
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Journal Title
Surgical Neurology International
Volume: 13
Pages: 372-372
DOI
Related Report
Peer Reviewed / Open Access
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