Interaction of Platelets with Ovarian Carcinoma Cells Leads to Induction of an Epithelial-Mesenchymal-Transition (EMT)-Associated Gene Expression Profile in Carcinoma Cells
Niamh Conlon, Cathy Spillane, Niamh Cooke, Sharon O'Toole, Cara Martin, Orla Sheils, Dermot Kenny, Michael Berndt, John O'Leary. St James's Hospital, Dublin, Ireland; Coombe Women and Infants University Hospital, Dublin, Ireland; University of Dublin, Trinity College, Dublin, Ireland; Dublin City University, Dublin, Ireland; Royal College of Surgeons Ireland, Dublin, Ireland
Background: While the relationship between malignancy and thrombosis has been recognised for centuries, the role of platelets in tumor growth and metastasis has been unclear. An association between malignancy and thrombocytosis has been noted in most solid tumor types, while the presence of induced thrombocytopenia in mouse models has been associated with a reduction in tumor metastasis. EMT represents the first step in the metastatic cascade in tumor cells, when they break free from their epithelial bindings and become primed for invasion. The expression of an EMT phenotype in carcinoma cells has been associated with increased cell survival, greater drug resistance and elevated metastatic potential. A recent study demonstrated that direct exposure to platelets in vitro caused induction of an EMT-associated gene-expression profile in two human breast cancer cell-lines. To date, this has not been demonstrated in any other subtype of human carcinoma. The aim of this study was to investigate whether direct interaction between ovarian carcinoma cells and platelets induced a similar EMT gene-expression signature.
Design: SKOV3 cells were seeded in 6-well plates and allowed to adhere overnight, followed by incubation with platelets.At the 24 hour time point, cells were harvested, RNA was extracted and gene expression analysis was performed using real time Taqman polymerase chain reaction (PCR) on a panel of EMT-associated markers.
Results: The adhesion of platelets to SKOV3 ovarian carcinoma cells resulted in the induction of an EMT phenotype. Gene expression analysis demonstrated changes in expression of EMT markers, including an increased expression of PAI-1 (Serpine 1), Snail, Slug and Vimentin, and reduced expression of epithelial cell markers E-cadherin and Claudin.
Conclusions: The direct interaction of platelets and ovarian carcinoma cells in vitro leads to induction of an EMT-like gene expression profile in ovarian carcinoma cells. This study demonstrates that this effect is not limited to breast carcinoma cells, and is likely to be a common feature of many forms of carcinoma. These results suggest a role for platelets in maximising the survival of metastatic carcinoma cells within the bloodstream, augmenting their ability to establish distant metastases.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 190, Wednesday Afternoon