Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor - PubMed (original) (raw)

. 2013 Jul 8;24(1):130-7.

doi: 10.1016/j.ccr.2013.05.008. Epub 2013 Jun 27.

Affiliations

• PMID: 23810565
• DOI: 10.1016/j.ccr.2013.05.008

Free article

Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor

Dagmar Schumacher et al. Cancer Cell. 2013.

Free article

Abstract

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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Comment in

• Metastasis: Exit this way.
  Alderton GK. Alderton GK. Nat Rev Cancer. 2013 Aug;13(8):523. doi: 10.1038/nrc3571. Epub 2013 Jul 18. Nat Rev Cancer. 2013. PMID: 23864051 No abstract available.
• Comment on "Platelet-derived nucleotides promote tumor cell transendothelial migration and metastasis via P2Y2 receptor" by Schumacher et al.
  Harper MT, Savage JS, Poole AW. Harper MT, et al. Cancer Cell. 2013 Sep 9;24(3):287. doi: 10.1016/j.ccr.2013.08.016. Cancer Cell. 2013. PMID: 24029227 No abstract available.
• Response to Harper et al.
  Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S. Schumacher D, et al. Cancer Cell. 2013 Sep 9;24(3):288. doi: 10.1016/j.ccr.2013.08.015. Cancer Cell. 2013. PMID: 24029228 No abstract available.

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