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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682154.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor
Authors:Schumacher, D.; Strilic, B.; Sivaraj, K. K.; Wettschureck, N.; Offermanns, S.
Date of Publication (YYYY-MM-DD):2013-07-08
Journal Abbrev.:Cancer Cell
Volume:24
Issue / Number:1
Start Page:130
End Page:137
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Adenosine Triphosphate/*physiology; Animals; Blood Platelets/*physiology; *Cell Movement; Cytoplasmic Granules/physiology; Endothelial Cells/*physiology; Humans; Mice; *Neoplasm Metastasis; Neoplasms/*pathology; Receptors, Purinergic P2Y2/*physiology
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1878-3686 (Electronic) 1535-6108 (Linking) %R 10.1016/j.ccr.2013.05.008
URL:http://www.ncbi.nlm.nih.gov/pubmed/23810565
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