2013 Fiscal Year Final Research Report
Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells.
| Project/Area Number |
23592073
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Kitasato University |
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Principal Investigator |
AMANO Hideki 北里大学, 医学部, 講師 (60296481)
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| Co-Investigator(Kenkyū-buntansha) |
ESHIMA Koji 北里大学, 医学部, 准教授 (30327324)
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| Project Period (FY) |
2011 – 2013
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| Keywords | Angiotensin II / AT1a receptor / platelets |
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| Research Abstract |
Angiotensin II is involved in tumor growth, however, the precise mechanism is not known. B16F1 melanoma cells were intravenously injected into Agtr1a knockout mice (AT1a(-/-)) and wild-type littermates (WT); the AT1a(-/-) mice exhibited a reduction in lung colonies. Angiotensin II induced expression of P-selectin on platelets in WT but not in AT1a(-/-) mice. A selective P-selectin neutralizing antibody decreased lung colony numbers in WT but not in AT1a(-/-) mice. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) receptor in platelets at metastatic locus were lower in AT1a(-/-) mice. Treatment of neutralizing antibodies against VEGF and CXCR4 decreased lung colony numbers in WT but not in AT1a(-/-) mice. In AT1a(-/-) mice. These results suggest that AT1A signaling plays a critical role in tumor metastasis through P-selectin-mediated interactions of platelets with tumor and endothelial cells.
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Research Products
(14 results)
