high-throughput screening for tumor endothelial cell specific inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02891
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Hokkaido University
• Principal Investigator: Hida Yasuhiro 北海道大学, 大学病院, 准教授 (30399919)
• Co-Investigator(Kenkyū-buntansha): 菊地 奈湖 (間石奈湖) 北海道大学, 歯学研究院, 助教 (00632423) ; 樋田 京子 北海道大学, 歯学研究院, 教授 (40399952)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 血管新生

Outline of Final Research Achievements

Tumor endothelial cells from human clinical tumors and normal endothelial cells from non-cancerous portions were isolated and cultured. FACS analysis and RT-PCR confirmed the establishment of highly pure primary cultured cells. The hTERT gene was transfected into these primary cultured cells, and more than 50 generations of passages were possible. The transgenic cells maintained a endothelial cell phenotype. The transgenic cells retained the phenotype of endothelial cells and the characteristic differences in gene expression observed in primary cultured cells were also retained, and it was confirmed that the cells met the conditions for use in cell-based high through-put assays. We are validating the inhibitors found by screening and verifying in the preclinical models.

Free Research Field

悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

血管新生阻害剤はさまざまな固形癌の治療に使用されているが，分子標的であるVEGFやVEGF受容体は正常血管内皮細胞の保持に必須な分子であるために，高血圧，出血，創傷治癒遅延などの副作用が不可避である点が課題として残っている．本研究では正常血管内皮細胞と腫瘍血管内皮細胞の違いを利用してhigh-through put screeningで腫瘍血管内皮細胞特異的な阻害剤を探索する手法を確立出来た．今後理想的な次世代腫瘍血管新生阻害の開発に寄与することが期待している．