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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells

Authors: Renan Orellana, Sumie Kato, Rafaela Erices, María Loreto Bravo, Pamela Gonzalez, Bárbara Oliva, Sofía Cubillos, Andrés Valdivia, Carolina Ibañez, Jorge Brañes, María Isabel Barriga, Erasmo Bravo, Catalina Alonso, Eva Bustamente, Enrique Castellon, Patricia Hidalgo, Cesar Trigo, Olga Panes, Jaime Pereira, Diego Mezzano, Mauricio A Cuello, Gareth I Owen

Published in: BMC Cancer | Issue 1/2015

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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.
Appendix
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Metadata
Title
Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
Authors
Renan Orellana
Sumie Kato
Rafaela Erices
María Loreto Bravo
Pamela Gonzalez
Bárbara Oliva
Sofía Cubillos
Andrés Valdivia
Carolina Ibañez
Jorge Brañes
María Isabel Barriga
Erasmo Bravo
Catalina Alonso
Eva Bustamente
Enrique Castellon
Patricia Hidalgo
Cesar Trigo
Olga Panes
Jaime Pereira
Diego Mezzano
Mauricio A Cuello
Gareth I Owen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1304-z

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