Exploration of pericyte-derived factors implicated in lung cancer brain metastasis protection; a pilot messenger RNA sequencing using the blood-brain barrier in vitro model.
| Project/Area Number |
17K10839
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Nagasaki University |
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Principal Investigator |
UJIFUKU Kenta 長崎大学, 医歯薬学総合研究科(医学系), 助教 (20437867)
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| Co-Investigator(Kenkyū-buntansha) |
松尾 孝之 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00274655)
吉田 光一 長崎大学, 病院(医学系), 助教 (20393457)
馬場 史郎 長崎大学, 病院(医学系), 助教 (30530430)
鎌田 健作 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (30549655)
諸藤 陽一 長崎大学, 病院(医学系), 助教 (40437869)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 転移性脳腫瘍 / 脳血液関門 / 初代培養細胞 / BBBキット / in vitro実験モデル / 肺がん / 脳神経疾患 |
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| Outline of Final Research Achievements |
The blood-brain barrier (BBB) implication is supposed to play a major role in brain metastasis. We applied an in vitro BBB model with rat primary cultured BBB-related cells (endothelial cells and pericytes), performed the gene expression analyses of pericytes under the lung cancer cells coculture conditions. Pericytes demonstrated inhibition of the cancer cell proliferation significantly. RNA was extracted from the pericytes and RNA-seq was performed. Lot-specific DEG detection demonstrated significant decreases in the expression of two genes (Wwtr1 and Acin1), and enrichment analyses revealed the inhibition of apoptotic processes in fibroblasts. Our results suggest that the expression profiles of brain pericytes are partially implicated in the prevention of lung cancer metastasis to the brain. Pericytes exerted an anti-metastatic effect in the BBB model, and their neurohumoral factors remain to be elucidated.
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| Academic Significance and Societal Importance of the Research Achievements |
ペリサイトが転移性脳腫瘍の成立に対して抑制的に働いていることが示唆された。また網羅的遺伝子解析を用いて、その機能の一部の解明を目指した基盤研究を実行することができた。炎症性サイトカイン以外の未知の液性因子が、がんの脳転移抑制に関与する可能性が示唆され、その関連遺伝子の有力な候補としてYAP-TAZ pathwayや線維芽細胞に関連する生命現象が挙げられると判明した。今後もIn vitro血液脳関門モデルを用いてその関連遺伝子に関わるメカニズムの解明を目指し、生命現象の解明のみならず、新規治療法の開発につながる知見が獲得できるのではないかと期待している。
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] MRNA-SEQ FOR PERICYTES FROM IN VITRO BRAIN METASTASIS AND BLOOD-BRAIN BARRIER MODEL.2020
Author(s)
Ujifuku, K., Fujimoto, T., Sato, K., Morofuji, Y., Muto, H., Masumoto, H., Nakagawa, S., Niwa, M., Matsuo, T.
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Journal Title
Neuro-Oncology Advances
Volume: 1(Supplement 2)
Issue: Supplement_2
Pages: ii11-ii11
DOI
Related Report
Open Access
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[Journal Article] Pericytes Suppress Brain Metastasis from Lung Cancer In Vitro.2019
Author(s)
Fujimoto, T., Nakagawa, S., Morofuji, Y., Watanabe, D., Ujifuku, K., Horie, N., Izumo, T., Niwa, M., Banks, W. A., Deli, M. A., Matsuo, T.
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Journal Title
Cell Mol Neurobiol
Volume: 40(1)
Issue: 1
Pages: 113-121
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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