A novel approach for cancer treatment based on homeostatic regulation of vascular system

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460337
• 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, 医学系研究科, 研究員 (50507506)
• Co-Investigator(Renkei-kenkyūsha): TANIGUCHI Shun'ichiro 信州大学, 医学部, 特任教授 (60117166)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血管新生

Outline of Final Research Achievements

In this study, we used inducible vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-) to clarify the contribution made by the endogenous RAMP2 to tumor angiogenesis and metastasis. Subcutaneously transplanted melanoma cells showed less angiogenesis in DI-E-RAMP2-/- than control mice. On the other hand, after transplantation of melanoma cells into hindlimb footpads, spontaneous metastasis to the lung was enhanced in DI-E-RAMP2-/-. Within the lungs of DI-E-RAMP2-/-, pulmonary endothelial cells were deformed, vascular permeability was enhanced, and inflammatory cells infiltrated the vessel walls and expressed the chemotactic factors S100A8/9 and SAA3, which attract tumor cells and mediate formation of a pre-metastatic niche.
These findings indicate that vascular RAMP2 deletion promotes formation of pre-metastatic niche in distant organs by destabilizing the vascular structure and inducing vascular inflammation.

Free Research Field

循環病態学