Platelet Modulation in the Control of Breast Cancer Angiogenesis and Metastasis

摘要

Platelets are circulating reservoirs of proteins that both promote and inhibit angiogenesis and metastasis. The release of proteins in the tumor microenvironment can be accomplished by multiple different pathways. We determined the influence of key platelet activation pathways on angiogenesis using an endothelial cell migration assay. We found independent pathways of platelet activation resulted in differential effects on angiogenesis. Activation through the platelet collagen receptor and proteinase activated receptor-4 (PAR4) receptor resulted in significantly increased endothelial cell migration while proteinase activated receptor-1 (PAR1) receptor stimulation did not increase endothelial cell migration. The endothelial cell migration effects did not correlate directly with the amount of platelet VEGF release suggesting additional platelet proteins are important in the release reaction and subsequent angiogenesis effects. Our results suggest targeted inhibition of collagen and PAR4 receptor mediated platelet activation may decrease angiogenesis in the tumor microenvironment. Our work identifies potential new targets for angiogenesis and cancer control in cells not previously targeted in breast cancer therapy. The ability to manipulate and control a large, circulating pool of angiogenesis and metastasis modulating proteins may represent a significant step forward in breast cancer control.