title: Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells.
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.
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. rorellanaw@gmail.com.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. rorellanaw@gmail.com.
authors.forename: Renan
authors.initials: R
authors.lastname: Orellana
authors.affiliation: Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile. skato@med.puc.cl.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. skato@med.puc.cl.
authors.forename: Sumie
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile. raerices@uc.cl.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. raerices@uc.cl.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Erices
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. marialoretobravo@gmail.com.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. marialoretobravo@gmail.com.
authors.forename: María Loreto
authors.initials: ML
authors.lastname: Bravo
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. pagonzax@puc.cl.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. pagonzax@puc.cl.
authors.forename: Pamela
authors.initials: P
authors.lastname: Gonzalez
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. barbara.oliva@gmail.com.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. barbara.oliva@gmail.com.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Oliva
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. smcubill@uc.cl.
authors.forename: Sofía
authors.initials: S
authors.lastname: Cubillos
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. aevaldiv@uc.cl.
authors.forename: Andrés
authors.initials: A
authors.lastname: Valdivia
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. cibanez@med.puc.cl.|Center UC Investigation in Oncology, Santiago, Chile. cibanez@med.puc.cl.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ibañez
authors.affiliation: Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile. jbranes@med.puc.cl.
authors.forename: Jorge
authors.initials: J
authors.lastname: Brañes
authors.affiliation: Hospital Sótero del Rio, Av. Concha y Toro 3459, Puente Alto, Santiago, Chile. ibarrigac@gmail.com.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Barriga
authors.affiliation: Hospital Gustavo Fricke, Viña de Mar, Santiago, Chile. erasmobravo@gmail.com.
authors.forename: Erasmo
authors.initials: E
authors.lastname: Bravo
authors.affiliation: Hospital Gustavo Fricke, Viña de Mar, Santiago, Chile. cataalonsomonte@gmail.com.
authors.forename: Catalina
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Fundación Arturo López Pérez, Av. Rancagua 878, Providencia, Santiago, Chile. bustamantee@falp.org.
authors.forename: Eva
authors.initials: E
authors.lastname: Bustamente
authors.affiliation: Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile Avda, Independencia 1027, Santiago, Chile. ecastell@med.uchile.cl.
authors.forename: Enrique
authors.initials: E
authors.lastname: Castellon
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. phidalgo@med.puc.cl.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hidalgo
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. cesar.trigo@yahoo.com.
authors.forename: Cesar
authors.initials: C
authors.lastname: Trigo
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. opanes@med.puc.cl.
authors.forename: Olga
authors.initials: O
authors.lastname: Panes
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. jpereira@med.puc.cl.
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.affiliation: Division de Hematology & Oncology, Faculty of Medicine, Santiago, Chile. dmezzano@med.puc.cl.|Center UC Investigation in Oncology, Santiago, Chile. dmezzano@med.puc.cl.
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
authors.affiliation: Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile, Santiago, Chile. macuello@med.puc.cl.|Center UC Investigation in Oncology, Santiago, Chile. macuello@med.puc.cl.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. macuello@med.puc.cl.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Cuello
authors.affiliation: Departament of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile. gowen@bio.puc.cl.|Center UC Investigation in Oncology, Santiago, Chile. gowen@bio.puc.cl.|Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile. gowen@bio.puc.cl.|Biomedical Research Consortium of Chile, Alameda 440, Piso 13, Santiago, Chile. gowen@bio.puc.cl.
authors.forename: Gareth I
authors.initials: GI
authors.lastname: Owen
mesh_terms: D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D002450:Cell Communication; D002465:Cell Movement; D002630:Chemotactic Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D015415:Biomarkers; D002630:Chemotactic Factors; D019038:Platelet Glycoprotein GPIb-IX Complex; D013925:Thromboplastin