Journal
CANCER CELL
Volume 24, Issue 1, Pages 130-137Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2013.05.008
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- Transregional Collaborative Research Center of the German Research Foundation [23, SFB/TR23]
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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 P2Y(2) receptor, which is activated by ATP, as the primary mediator of this effect. Mice deficient in P2Y(2) 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 P2Y(2) receptor and its endothelial downstream signaling mechanisms as a target for antimetastatic therapies.
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