Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells.

Authors:
Karl Egan
Karl Egan
Royal College of Surgeons in Ireland
Ireland
Paul Smyth
Paul Smyth
Dartmouth Medical School
United States
Cathy Spillane
Cathy Spillane
Trinity College Dublin
Ireland
Cara Martin
Cara Martin
Trinity College Dublin
Ireland
Michael Gallagher
Michael Gallagher
William Beaumont Hospital
United States
Aoife Canney
Aoife Canney
St Vincent's University Hospital

PLoS One 2011 12;6(10):e26125. Epub 2011 Oct 12.

Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland.

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.

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026125PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192146PMC
February 2012
20 Reads
41 PubMed Central Citations(source)
3.23 Impact Factor

Publication Analysis

Top Keywords

ovarian cancer
36
cancer cells
28
platelet activation
12
59m cell
12
cancer
9
cells
9
ovarian
9
platelet
8
59m cells
8
platelets platelet
8
receptor mediated
8
platelet releasate
8
induced activation
8
pro-survival pro-angiogenic
8
activation
6
59m
6
platelets
5
adp 59m
4
release adp
4
activation dependent
4

Similar Publications

Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion.

BMC Cancer 2015 Sep 9;15:627. Epub 2015 Sep 9.

Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland.

Background: Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. Read More

View Article
September 2015

Potentiation of platelet aggregation by heparin in human whole blood is attenuated by P2Y12 and P2Y1 antagonists but not aspirin.

Thromb Res 2005 ;115(4):301-7

Cardiovascular Research Unit, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, UK.

Introduction: Unfractionated heparin (UFH) potentiates platelet aggregation induced by some agonists. P2Y12 and P2Y1 receptors play a major role in amplifying platelet aggregation. We assessed the ability of cangrelor, a selective P2Y12 antagonist, A2P5P, a selective P2Y1 antagonist, and aspirin to block the potentiating effects of heparin. Read More

View Article
August 2005

On the mechanism of plasmin-induced platelet aggregation. Implications of the dual role of granule ADP.

Biochem Pharmacol 2000 Jun;59(11):1345-55

Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan.

Plasmin-induced platelet aggregation has been considered to be a cause of reocclusion after thrombolytic treatment with plasminogen activators. However, little is known regarding the mechanism and regulation of plasmin-induced platelet aggregation. In this study, we demonstrated that plasmin causes the degranulation of platelets, and that ADP released from granules plays a crucial role in the induction of platelet aggregation. Read More

View Article
June 2000

Deciphering of ADP-induced, phosphotyrosine-dependent signaling networks in human platelets by Src-homology 2 region (SH2)-profiling.

Proteomics 2013 Mar 18;13(6):1016-27. Epub 2013 Feb 18.

Institute of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Tyrosine phosphorylation plays a central role in signal transduction controlling many important biological processes. In platelets, the activity of several signaling proteins is controlled by tyrosine phosphorylation ensuring proper platelet activation and aggregation essential for regulation of the delicate balance between bleeding and hemostasis. Here, we applied Src-homology 2 region (SH2)-profiling for deciphering of the phosphotyrosine state of human platelets activated by adenosine diphosphate (ADP). Read More

View Article
March 2013