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

Althawadi H, Alfarsi H, Besbes S, Mirshahi S, Ducros E, Rafii A, Pocard M, Therwath A, Soria J, Mirshahi M - Oncol. Rep. (2015)

Bottom Line: 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.This binding could also explain the loss of clotting of peritoneal fluids.

View Article: PubMed Central - PubMed

Affiliation: UMR, Paris Diderot, Paris 7 University, Lariboisiere Hospital, INSERM U965, Paris, France.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Influence of aPC and PC on ovarian cancer cell migration. (A) Results after 24 h compared with 0 h. (B) An increase in cell migration was induced by aPC at all time-lapses of the experiment. PC, protein C; aPC, active protein C.
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f2-or-34-02-0603: Influence of aPC and PC on ovarian cancer cell migration. (A) Results after 24 h compared with 0 h. (B) An increase in cell migration was induced by aPC at all time-lapses of the experiment. PC, protein C; aPC, active protein C.

Mentions: The influence of protein C on OVCAR-3 cell migration at 3, 6, 9 and 24 h is presented in Fig. 2. It was observed that aPC enhanced cell migration into the wound, whereas in the presence of PC, cell migration was found to be similar to that of the control. The histogram in Fig. 2B depicts the effect of aPC and PC on ovarian cancer cells migrating into the scar region as a function of time (0, 3, 6, 9 and 24 h).


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

Althawadi H, Alfarsi H, Besbes S, Mirshahi S, Ducros E, Rafii A, Pocard M, Therwath A, Soria J, Mirshahi M - Oncol. Rep. (2015)

Influence of aPC and PC on ovarian cancer cell migration. (A) Results after 24 h compared with 0 h. (B) An increase in cell migration was induced by aPC at all time-lapses of the experiment. PC, protein C; aPC, active protein C.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487670&req=5

f2-or-34-02-0603: Influence of aPC and PC on ovarian cancer cell migration. (A) Results after 24 h compared with 0 h. (B) An increase in cell migration was induced by aPC at all time-lapses of the experiment. PC, protein C; aPC, active protein C.
Mentions: The influence of protein C on OVCAR-3 cell migration at 3, 6, 9 and 24 h is presented in Fig. 2. It was observed that aPC enhanced cell migration into the wound, whereas in the presence of PC, cell migration was found to be similar to that of the control. The histogram in Fig. 2B depicts the effect of aPC and PC on ovarian cancer cells migrating into the scar region as a function of time (0, 3, 6, 9 and 24 h).

Bottom Line: 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.This binding could also explain the loss of clotting of peritoneal fluids.

View Article: PubMed Central - PubMed

Affiliation: UMR, Paris Diderot, Paris 7 University, Lariboisiere Hospital, INSERM U965, Paris, France.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus