Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells.
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.
Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Karl
K
Egan
Darragh
D
Crowley
Paul
P
Smyth
Sharon
S
O'Toole
Cathy
C
Spillane
Cara
C
Martin
Michael
M
Gallagher
Aoife
A
Canney
Lucy
L
Norris
Niamh
N
Conlon
Lynda
L
McEvoy
Brendan
B
Ffrench
Britta
B
Stordal
Helen
H
Keegan
Stephen
S
Finn
Victoria
V
McEneaney
Alex
A
Laios
Jens
J
Ducrée
Eimear
E
Dunne
Leila
L
Smith
Michael
M
Berndt
Orla
O
Sheils
Dermot
D
Kenny
John
J
O'Leary
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D001081:Apyrase / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D010446:Peptide Fragments; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin; C086309:thrombin receptor peptide SFLLRNP; D016718:Arachidonic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C117446:cangrelor; D000255:Adenosine Triphosphate; D001081:Apyrase; C112908:protease-activated receptor 4