Browsing by Author "González Hevia, Pamela Andrea."

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    Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells.
    (2015) Orellana, Renan.; Kato Cardemil, Sumie Rode; Erices, Rafaela.; Bravo Castillo, María Loreto; González Hevia, Pamela Andrea.; Oliva, Bárbara.; Cubillos Alfaro, Sofía María Jesús.; Valdivia Román, Andrés Felipe; Brañes, Jorge; Cuello F., Mauricio; Ibañez, Carolina; Barriga Cosmelli, María Isabel; Bravo, Erasmo.; Alonso, Catalina.; Bustamente, Eva.; Castellon, Enrique.; Hidalgo, Patricia.; Trigo, Cesar.; Panes Becerra, Olga Teresa; Pereira Garcés, Jaime Ignacio; Mezzano, Diego; Owen, Gareth Ivor
    Abstract Background An increase in circulating platelets, or thrombocytosis, is recognized as an independent risk factor of bad prognosis and metastasis in patients with ovarian cancer; however the complex role of platelets in tumor progression has not been fully elucidated. Platelet activation has been associated with an epithelial to mesenchymal transition (EMT), while Tissue Factor (TF) protein expression by cancer cells has been shown to correlate with hypercoagulable state and metastasis. The aim of this work was to determine the effect of platelet-cancer cell interaction on TF and “Metastasis Initiating Cell (MIC)” marker levels and migration in ovarian cancer cell lines and cancer cells isolated from the ascetic fluid of ovarian cancer patients. Methods With informed patient consent, ascitic fluid isolated ovarian cancer cells, cell lines and ovarian cancer spheres were co-cultivated with human platelets. TF, EMT and stem cell marker levels were determined by Western blotting, flow cytometry and RT-PCR. Cancer cell migration was determined by Boyden chambers and the scratch assay. Results The co-culture of patient-derived ovarian cancer cells with platelets causes: 1) a phenotypic change in cancer cells, 2) chemoattraction and cancer cell migration, 3) induced MIC markers (EMT/stemness), 3) increased sphere formation and 4) increased TF protein levels and activity. Conclusions We present the first evidence that platelets act as chemoattractants to cancer cells. Furthermore, platelets promote the formation of ovarian cancer spheres that express MIC markers and the metastatic protein TF. Our results suggest that platelet-cancer cell interaction plays a role in the formation of metastatic foci.