Establishment of a novel anti-angiogenic treatment targeting Tumor endothelial cell specific non-coding RNA

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15831
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kurume University
• Principal Investigator: Hideki Iwamoto 久留米大学, 医学部, 助教 (40529541)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 癌血管 / マイクロRNA / 肝細胞癌

Outline of Final Research Achievements

It is known that tumor endothelial cells (TECs) are functionally and genetically different from normal ECs. In this study, we have clarified morphologic, functional, and genetic differences between TEC and liver sinusoidal endothelial cells (LSEC) to find a specific molecular target that can only inhibit tumor angiogenesis without inhibition of normal vessels. In the study, TEC showed disorganized, leaky, and less perfused vessels, compared with LSECs, which resulted in increased hypoxia within tumors. We have detected the top 5 downregulated TEC-specific miRs. Downregulation of TEC-specific miRs showed significantly increased tube formation. Notably, TEC-specific miRs agonists significantly inhibited tumor growth in HCC orthotopic model mice with only inhibiting tumor vessels. Our detected TEC-specific miRs were strongly correlated with tumor angiogenesis, which can be novel and promising therapeutic targets for HCC.

Free Research Field

肝細胞癌

Academic Significance and Societal Importance of the Research Achievements

本研究の新規性として、一つ目は癌血管に特異的なマイクロRNAの発見が挙げられる。二つ目は、同定されたマイクロRNAを制御する事で癌血管のみを抑制する事ができるという点である。現在、癌血管を標的とした治療は、様々な癌種の標準的な治療であり、その治療における問題点を本研究では解決した。従って、本研究の達成による癌患者への貢献は大きいものと考える。また、遺伝子導入により癌治療を行う事は、今後の癌治療の大きな進歩の一つであり、本研究の達成により新たな可能性が見いだされた。