Activated platelets secrete both α-granules and dense granules, and it has been suggested that factors stored in these granules might facilitate metastasis. So, Offermanns and colleagues investigated whether these platelet-derived granules facilitate the extravasation of disseminated tumour cells through the endothelium. They showed that tumour cell migration through endothelial cells in an in vitro assay was dependent on secreted factors from platelets, which were activated by co-incubation with various tumour cell lines. Further investigation revealed that platelet-derived adenine nucleotides, which are stored in dense granules, were responsible for this effect and that they also resulted in the opening of the endothelial barrier (through the loss of junctional contacts). Next, the authors made use of a transgenic mouse model, MUNC13-4-deficient mice, which have platelets that are unable to secrete dense granules. They found that subcutaneous injection of B16 melanoma and Lewis lung carcinoma (LLC1) cells into these mice resulted in the formation of primary tumours to the same extent as in wild-type mice but that the number of metastases was significantly reduced in MUNC13-4-deficient mice. Numbers of metastases were also significantly reduced when these cells were injected into the tail vein of MUNC13-4-deficient mice.
tumour cell-activated platelets secrete adenine nucleotides, which ... induce the opening of the endothelial barrier
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