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Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment

The objective of this study was to evaluate the role of activated protein C (aPC), known to be a physiological anticoagulant, in ovarian cancer cell activation as well as in loss of clotting of cancer ascitic fluid. The effect of aPC on an ovarian cancer cell line (OVCAR-3) was tested in regards to...

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Autores principales: ALTHAWADI, HAMDA, ALFARSI, HALEMA, BESBES, SAMAHER, MIRSHAHI, SHAHSOLTAN, DUCROS, ELODIE, RAFII, ARASH, POCARD, MARC, THERWATH, AMU, SORIA, JEANNETTE, MIRSHAHI, MASSOUD
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487670/
https://www.ncbi.nlm.nih.gov/pubmed/26082331
http://dx.doi.org/10.3892/or.2015.4061
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author ALTHAWADI, HAMDA
ALFARSI, HALEMA
BESBES, SAMAHER
MIRSHAHI, SHAHSOLTAN
DUCROS, ELODIE
RAFII, ARASH
POCARD, MARC
THERWATH, AMU
SORIA, JEANNETTE
MIRSHAHI, MASSOUD
author_facet ALTHAWADI, HAMDA
ALFARSI, HALEMA
BESBES, SAMAHER
MIRSHAHI, SHAHSOLTAN
DUCROS, ELODIE
RAFII, ARASH
POCARD, MARC
THERWATH, AMU
SORIA, JEANNETTE
MIRSHAHI, MASSOUD
author_sort ALTHAWADI, HAMDA
collection PubMed
description The objective of this study was to evaluate the role of activated protein C (aPC), known to be a physiological anticoagulant, in ovarian cancer cell activation as well as in loss of clotting of cancer ascitic fluid. The effect of aPC on an ovarian cancer cell line (OVCAR-3) was tested in regards to i) cell migration and adhesion with the use of adhesion and wound healing assays as well as a droplet test; ii) protein phosphorylation, evaluated by cyto-ELISA; iii) cell cycle modification assessed by flow cytometric DNA quantification; and iv) anticoagulant activity evaluated by the prolongation of partial thromboplastin time (aPTT) of normal plasma in the presence or absence of aPC-treated ovarian cancer cells. In addition, the soluble endothelial protein C receptor (sEPCR) was quantified by ELISA in ascitic fluid of patients with ovarian cancer. Our results showed that in the OVCAR-3 aPC-induced cells i) an increase in cell migration was noted, which was inhibited when anti-endothelial protein C receptor (EPCR) was added to the culture medium and which may act via MEK-ERK and Rho-GTPase pathways; ii) an increase in threonine, and to a lesser extent tyrosine phosphorylation; iii) cell cycle activation (G1 to S/G2); and iv) a 2-3-fold prolongation of aPTT of normal plasma. In the peritoneal fluid, the sEPCR concentration was 71±23 ng/ml. In conclusion, free aPC binds to membrane EPCR in ovarian cancer cells and induces cell migration via MEK-ERK and Rho-GTPase pathways. This binding could also explain the loss of clotting of peritoneal fluids.
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spelling pubmed-44876702015-07-13 Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment ALTHAWADI, HAMDA ALFARSI, HALEMA BESBES, SAMAHER MIRSHAHI, SHAHSOLTAN DUCROS, ELODIE RAFII, ARASH POCARD, MARC THERWATH, AMU SORIA, JEANNETTE MIRSHAHI, MASSOUD Oncol Rep Articles The objective of this study was to evaluate the role of activated protein C (aPC), known to be a physiological anticoagulant, in ovarian cancer cell activation as well as in loss of clotting of cancer ascitic fluid. The effect of aPC on an ovarian cancer cell line (OVCAR-3) was tested in regards to i) cell migration and adhesion with the use of adhesion and wound healing assays as well as a droplet test; ii) protein phosphorylation, evaluated by cyto-ELISA; iii) cell cycle modification assessed by flow cytometric DNA quantification; and iv) anticoagulant activity evaluated by the prolongation of partial thromboplastin time (aPTT) of normal plasma in the presence or absence of aPC-treated ovarian cancer cells. In addition, the soluble endothelial protein C receptor (sEPCR) was quantified by ELISA in ascitic fluid of patients with ovarian cancer. Our results showed that in the OVCAR-3 aPC-induced cells i) an increase in cell migration was noted, which was inhibited when anti-endothelial protein C receptor (EPCR) was added to the culture medium and which may act via MEK-ERK and Rho-GTPase pathways; ii) an increase in threonine, and to a lesser extent tyrosine phosphorylation; iii) cell cycle activation (G1 to S/G2); and iv) a 2-3-fold prolongation of aPTT of normal plasma. In the peritoneal fluid, the sEPCR concentration was 71±23 ng/ml. In conclusion, free aPC binds to membrane EPCR in ovarian cancer cells and induces cell migration via MEK-ERK and Rho-GTPase pathways. This binding could also explain the loss of clotting of peritoneal fluids. D.A. Spandidos 2015-08 2015-06-15 /pmc/articles/PMC4487670/ /pubmed/26082331 http://dx.doi.org/10.3892/or.2015.4061 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
ALTHAWADI, HAMDA
ALFARSI, HALEMA
BESBES, SAMAHER
MIRSHAHI, SHAHSOLTAN
DUCROS, ELODIE
RAFII, ARASH
POCARD, MARC
THERWATH, AMU
SORIA, JEANNETTE
MIRSHAHI, MASSOUD
Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title_full Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title_fullStr Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title_full_unstemmed Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title_short Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
title_sort activated protein c upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487670/
https://www.ncbi.nlm.nih.gov/pubmed/26082331
http://dx.doi.org/10.3892/or.2015.4061
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