Karl Egan., Darragh Crowley., Paul Smyth, Sharon O Toole, Cathy Spillane, Cara Martin, Michael Gallagher, Aoife Canney, Lucy Norris, Niamh Conlon, Lynda McEvoy2, Brendan Ffrench2, Britta Stordal, Helen Keegan, Stephen Finn, Victoria McEneaney, Alex Laios, Jens Ducre, Eimear Dunne, Leila Smith, Michael Berndt, Orla Sheils, Dermot Kenny, John O Leary, Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells, PLoS ONE, 6, 10, e26125, 2011
PLoS ONE; 6; 10, e26125;
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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