Regulation of vascular homeostasis by AM-RAMP2 system and its therapeutic application for vascular abnormalities.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08588
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Shinshu University
• Principal Investigator: Shindo Yuka 信州大学, 医学部, 研究員 (50507506)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血管 / 血管新生 / 転移

Outline of Final Research Achievements

We have reported that vasoactive peptide adrenomedullin (AM) and its receptor activity-modifying protein RAMP2 possess angiogenic function and regulate vascular homeostasis. On the other hand, AM and RAMP2 are highly expressed in various cancers. In this study, using drug-inducible endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-), we analyzed the significance of AM-RAMP2 system in cancer angiogenesis and metastasis. In tumor implantation model, we found that angiogenesis of primary lesion was suppressed, whereas spontaneous lung metastasis was increased.
Vascular integrity regulated by the AM-RAMP2 system could thus be a hopeful therapeutic target for suppressing tumor metastasis.

Free Research Field

循環病態学

Academic Significance and Societal Importance of the Research Achievements

病的血管新生は、癌をはじめ、様々な疾患の発症や病態と深く関わっている。今回我々は、アドレノメデュリン(AM)-RAMP2 システムが、血管の恒常性維持に関わっている一方で、その破綻によって血管の恒常性が障害され、癌細胞が転移しやすい環境=転移前土壌が形成されることを見出した。AM-RAMP2系による血管恒常性維持作用に介入し、これを制御することは、従来の治療法とは異なり、癌腫を問わない治療法の開発につながる可能性がある。