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Hematology - Molecular Biology - Oncology


Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells
Published: Wednesday, October 12, 2011
Author: Karl Egan et al.

by Karl Egan, Darragh Crowley, Paul Smyth, Sharon O'Toole, Cathy Spillane, Cara Martin, Michael Gallagher, Aoife Canney, Lucy Norris, Niamh Conlon, Lynda McEvoy, Brendan Ffrench, Britta Stordal, Helen Keegan, Stephen Finn, Victoria McEneaney, Alex Laios, Jens Ducrée, Eimear Dunne, Leila Smith, Michael Berndt, Orla Sheils, Dermot Kenny, John O'Leary

Thrombosis is common in ovarian cancer. However, the interaction of platelets with ovarian cancer cells has not been critically examined. To address this, we investigated platelet interactions in a range of ovarian cancer cell lines with different metastatic potentials [HIO-80, 59M, SK-OV-3, A2780, A2780cis]. Platelets adhered to ovarian cancer cells with the most significant adhesion to the 59M cell line. Ovarian cancer cells induced platelet activation [P-selectin expression] in a dose dependent manner, with the most significant activation seen in response to the 59M cell line. The platelet antagonists [cangrelor, MRS2179, and apyrase] inhibited 59M cell induced activation suggesting a P2Y12 and P2Y1 receptor mediated mechanism of platelet activation dependent on the release of ADP by 59M cells. A2780 and 59M cells potentiated PAR-1, PAR-4, and TxA2 receptor mediated platelet activation, but had no effect on ADP, epinephrine, or collagen induced activation. Analysis of gene expression changes in ovarian cancer cells following treatment with washed platelets or platelet releasate showed a subtle but valid upregulation of anti-apoptotic, anti-autophagy pro-angiogenic, pro-cell cycle and metabolic genes. Thus, ovarian cancer cells with different metastatic potential adhere and activate platelets differentially while both platelets and platelet releasate mediate pro-survival and pro-angiogenic signals in ovarian cancer cells.
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