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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

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 ass...

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Autores principales: Orellana, Renan, Kato, Sumie, Erices, Rafaela, Bravo, María Loreto, Gonzalez, Pamela, Oliva, Bárbara, Cubillos, Sofía, Valdivia, Andrés, Ibañez, Carolina, Brañes, Jorge, Barriga, María Isabel, Bravo, Erasmo, Alonso, Catalina, Bustamente, Eva, Castellon, Enrique, Hidalgo, Patricia, Trigo, Cesar, Panes, Olga, Pereira, Jaime, Mezzano, Diego, Cuello, Mauricio A, Owen, Gareth I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410584/
https://www.ncbi.nlm.nih.gov/pubmed/25886038
http://dx.doi.org/10.1186/s12885-015-1304-z
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author Orellana, Renan
Kato, Sumie
Erices, Rafaela
Bravo, María Loreto
Gonzalez, Pamela
Oliva, Bárbara
Cubillos, Sofía
Valdivia, Andrés
Ibañez, Carolina
Brañes, Jorge
Barriga, María Isabel
Bravo, Erasmo
Alonso, Catalina
Bustamente, Eva
Castellon, Enrique
Hidalgo, Patricia
Trigo, Cesar
Panes, Olga
Pereira, Jaime
Mezzano, Diego
Cuello, Mauricio A
Owen, Gareth I
author_facet Orellana, Renan
Kato, Sumie
Erices, Rafaela
Bravo, María Loreto
Gonzalez, Pamela
Oliva, Bárbara
Cubillos, Sofía
Valdivia, Andrés
Ibañez, Carolina
Brañes, Jorge
Barriga, María Isabel
Bravo, Erasmo
Alonso, Catalina
Bustamente, Eva
Castellon, Enrique
Hidalgo, Patricia
Trigo, Cesar
Panes, Olga
Pereira, Jaime
Mezzano, Diego
Cuello, Mauricio A
Owen, Gareth I
author_sort Orellana, Renan
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1304-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-44105842015-04-28 Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells Orellana, Renan Kato, Sumie Erices, Rafaela Bravo, María Loreto Gonzalez, Pamela Oliva, Bárbara Cubillos, Sofía Valdivia, Andrés Ibañez, Carolina Brañes, Jorge Barriga, María Isabel Bravo, Erasmo Alonso, Catalina Bustamente, Eva Castellon, Enrique Hidalgo, Patricia Trigo, Cesar Panes, Olga Pereira, Jaime Mezzano, Diego Cuello, Mauricio A Owen, Gareth I BMC Cancer Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1304-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-15 /pmc/articles/PMC4410584/ /pubmed/25886038 http://dx.doi.org/10.1186/s12885-015-1304-z Text en © Orellana et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Orellana, Renan
Kato, Sumie
Erices, Rafaela
Bravo, María Loreto
Gonzalez, Pamela
Oliva, Bárbara
Cubillos, Sofía
Valdivia, Andrés
Ibañez, Carolina
Brañes, Jorge
Barriga, María Isabel
Bravo, Erasmo
Alonso, Catalina
Bustamente, Eva
Castellon, Enrique
Hidalgo, Patricia
Trigo, Cesar
Panes, Olga
Pereira, Jaime
Mezzano, Diego
Cuello, Mauricio A
Owen, Gareth I
Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title_full Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title_fullStr Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title_full_unstemmed Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title_short Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
title_sort platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410584/
https://www.ncbi.nlm.nih.gov/pubmed/25886038
http://dx.doi.org/10.1186/s12885-015-1304-z
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