Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells.

血管紧张素II参与肿瘤生长，但其确切机制尚不清楚。将B16F1黑色素瘤细胞静脉注射到Agtr1a基因敲除小鼠（AT1a(-/-)）和野生型幼崽（WT）中；AT1a（-/-）小鼠肺菌落减少。血管紧张素II在WT小鼠血小板上诱导p -选择素的表达，而在AT1a（-/-）小鼠中不诱导。选择性p -选择素中和抗体可减少WT小鼠的肺集落数量，但在AT1a（-/-）小鼠中无此作用。AT1a（-/-）小鼠转移位点血小板中血管内皮生长因子（VEGF）和基质细胞衍生因子1 （SDF-1）受体水平较低。抗VEGF和CXCR4的中和抗体治疗可以减少WT小鼠的肺集落数量，但在AT1a（-/-）小鼠中没有。在AT1a（-/-）小鼠。这些结果表明AT1A信号通过p选择素介导的血小板与肿瘤和内皮细胞的相互作用在肿瘤转移中起关键作用。

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.