Cancer Cell
Volume 24, Issue 1, 8 July 2013, Pages 130-137
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Report
Platelet-Derived Nucleotides Promote Tumor-Cell Transendothelial Migration and Metastasis via P2Y2 Receptor

https://doi.org/10.1016/j.ccr.2013.05.008Get rights and content
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Highlights

  • Tumor cell-activated platelets facilitate tumor cell endothelial transmigration

  • Platelet-dependent tumor cell transmigration requires ATP released from platelets

  • Mice with defective platelet ATP secretion show reduced tumor cell metastasis

  • ATP-induced tumor cell extravasation and metastasis depends on the P2Y2 receptor

Summary

Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. The exact mechanisms by which platelets promote metastasis have remained unclear. Here, we show that adenine nucleotides released from tumor cell-activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and thereby promote cancer cell extravasation. We identified the endothelial P2Y2 receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y2 or lacking ATP secretion from platelets show strongly reduced tumor cell metastasis. These findings demonstrate a mechanism by which platelets promote cancer cell metastasis and suggest the P2Y2 receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.

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These authors contributed equally to this work