Platelet Adhesion and Degranulation Induce Pro-Survival and Pro-Angiogenic Signalling in Ovarian Cancer Cells

被引：151

作者：

Egan, Karl ^{[1
]}

Crowley, Darragh ^{[2
]}

Smyth, Paul ^{[2
]}

O'Toole, Sharon ^{[2
,3
]}

Spillane, Cathy ^{[2
]}

Martin, Cara ^{[2
]}

Gallagher, Michael ^{[2
]}

Canney, Aoife ^{[2
]}

Norris, Lucy ^{[3
]}

Conlon, Niamh ^{[2
]}

McEvoy, Lynda ^{[2
]}

Ffrench, Brendan ^{[2
]}

Stordal, Britta ^{[2
]}

Keegan, Helen ^{[2
]}

Finn, Stephen ^{[2
]}

McEneaney, Victoria ^{[2
]}

Laios, Alex ^{[2
,3
]}

Ducree, Jens ^{[4
]}

Dunne, Eimear ^{[1
]}

Smith, Leila ^{[5
]}

Berndt, Michael ^{[1
,4
]}

Sheils, Orla ^{[2
]}

Kenny, Dermot ^{[1
,4
]}

O'Leary, John ^{[2
]}

机构：

[1] Royal Coll Surgeons Ireland, Dublin 2, Ireland

[2] Trinity Coll Dublin, Dept Histopathol, Dublin, Ireland

[3] Trinity Coll Dublin, Dept Obstet & Gynaecol, Dublin, Ireland

[4] Dublin City Univ, Biomed Diagnost Inst, Dublin 9, Ireland

[5] Fluidigm Corp Europe, Amsterdam, Netherlands

来源：

PLOS ONE | 2011年 / 6卷 / 10期

基金：

爱尔兰科学基金会;

关键词：

GLYCOPROTEIN IB-ALPHA; EXPERIMENTAL LUNG METASTASIS; TUMOR-CELLS; DIMERIC BETA(2)-GLYCOPROTEIN-I; KALLIKREIN GENES; GROWTH-FACTOR; ACTIVATION; RECEPTORS; B7-H1; OVEREXPRESSION;

D O I：

10.1371/journal.pone.0026125

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：13

共 54 条

[1]

AITOKALLIOTALLBERG AM, 1988, CANCER RES, V48, P2396

[2]

Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients [J].