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

نویسندگان

  • HAMDA ALTHAWADI
  • HALEMA ALFARSI
  • SAMAHER BESBES
  • SHAHSOLTAN MIRSHAHI
  • ELODIE DUCROS
  • ARASH RAFII
  • MARC POCARD
  • AMU THERWATH
  • JEANNETTE SORIA
  • MASSOUD MIRSHAHI
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A Mimic of the Tumor Microenvironment on GPR30 Gene Expression in Breast Cancer

Introduction: The G-protein coupled receptor 30 (GPR30) gene is a member of the G-protein coupled receptor (GPCR) family; involved in breast, endometrial, and ovarian cancers. Many GPCR receptors that are implicated in several types of human cancers are correlated with increased cell proliferation and tumor progression; especially GPR30 gene. Methods: The breast cancer MCF-7 and MDA-MB-231 cel...

متن کامل

STAT3 as a Key Factor in Tumor Microenvironment and Cancer Stem Cell

Background Recent studies revealed that tumor-associated macrophages (TAMs) play a decisive role in the regulation of tumor progression by manipulating tumor oncogenesis, angiogenesis and immune functions within tumor microenvironments. Signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activ...

متن کامل

Effect of valproic acid on JAK/STAT pathway, SOCS1, SOCS3, Bcl-xL, c-Myc, and Mcl-1 gene expression, cell growth inhibition and apoptosis induction in human colon cancer HT29 cell line.

Background and aim: Cytokines are a large family of protein messengers. These proteins induce various cellular responses. Janus kinases (JAKs) are mediators of cytokine, activated JAKs phosphorylate signal transducers, and activators of transcription (STAT) proteins that regulate cell differentiation, proliferation, and apoptosis. Aberrant JAK/STAT signaling is involved in the oncogenesis of se...

متن کامل

shRNA-mediated downregulation of α-N-Acetylgalactosaminidase inhibits migration and invasion of cancer cell lines

Objective(s): Extracellular matrix (ECM) is composed of many kinds of glycoproteins containing glycosaminoglycans (GAGs) moiety. The research was conducted based on the N-Acetylgalactosamine (GalNAc) degradation of ECM components by α-N-acetylgalactosaminidase (Nagalase) which facilitates migration and invasion of cancer cells. This study aims to investigate the effects of Naga-shRNA downregula...

متن کامل

Gene Expression Changes in Pomegranate Peel Extract-Treated Triple-Negative Breast Cancer Cells

Background: Triple-negative breast cancer (TNBC) is treated with highly aggressive non-targeted chemotherapies. Safer and more effective therapeutic approaches than those currently in use are needed. Natural pomegranate peel extract (PPE) has recently been found to inhibit breast cancer progression; however, its mechanisms of action remain unclear. We hypothesized that transcriptional chan...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 34  شماره 

صفحات  -

تاریخ انتشار 2015