Platelets assist in extravasation

Platelets can be activated by tumour cells, but how they contribute to metastasis has been unclear. Offermans and colleagues now show that platelet activation by tumour cells facilitates transendothelial cell migration (Cancer Cell 24, 130–137; 2013).

By studying the transmigration of cancer cells through an endothelial cell layer in vitro, the authors found that cell lines derived from melanoma and lung carcinoma successfully migrated between the endothelial cells in the presence of either activated platelets or their supernatant. Degradation of platelet-derived nucleotides, such as ATP and ADP, inhibited transendothelial migration. These nucleotides are produced from dense granules that are released by active platelets. Blocking the release of these granules by using mice that lack the exocytosis-priming protein MUNC13-4 inhibited the transendothelial migration of the cancer cells from subcutaneous xenografts and after tail vein injection. The authors further showed that an adenosine receptor, P2Y₂, which is expressed on endothelial cells, is required for successful migration: mice lacking P2Y₂ in endothelial cells had reduced levels of pulmonary metastases compared with controls after tail vein injection of tumour cells. Platelet-derived ATP was found to cause a loss of tight interendothelial junctions, as shown by the leakage of labelled dextran across the lung endothelial cell barrier in vivo.

These findings raise the possibility that P2Y₂ and its associated signalling pathway could represent therapeutic targets, which remains a topic for further study.