Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Oncology Reports Année : 2015

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

Hamda Althawadi
  • Fonction : Auteur
Halema Alfarsi
  • Fonction : Auteur
Samaher Besbes
  • Fonction : Auteur
Shahsoltan Mirshahi
  • Fonction : Auteur
Elodie Ducros
  • Fonction : Auteur
Arash Rafii
  • Fonction : Auteur
Marc Pocard
Amu Therwath
  • Fonction : Auteur
Jeannette Soria
  • Fonction : Auteur
Massoud Mirshahi
  • Fonction : Auteur
  • PersonId : 975683

Résumé

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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Dates et versions

hal-03123258 , version 1 (27-01-2021)

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Paternité - Pas d'utilisation commerciale

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Citer

Hamda Althawadi, Halema Alfarsi, Samaher Besbes, Shahsoltan Mirshahi, Elodie Ducros, et al.. Activated protein C upregulates ovarian cancer cell migration and promotes unclottability of the cancer cell microenvironment. Oncology Reports, 2015, 34 (2), pp.603-609. ⟨10.3892/or.2015.4061⟩. ⟨hal-03123258⟩

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