| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| 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.
|
