Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis

<p>Abstract</p> <p>Background</p> <p>Resistance to apoptosis is a major problem in ovarian cancer and correlates with poor prognosis. Osteoprotegerin (OPG) is a secreted factor in malignant ascites and acts as a decoy receptor for receptor activator of NF-κB ligand (RAN...

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Main Authors: Lane Denis, Matte Isabelle, Rancourt Claudine, Piché Alain
Format: Article
Language:English
Published: BMC 2012-11-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://www.ovarianresearch.com/content/5/1/34
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author Lane Denis
Matte Isabelle
Rancourt Claudine
Piché Alain
author_facet Lane Denis
Matte Isabelle
Rancourt Claudine
Piché Alain
author_sort Lane Denis
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Resistance to apoptosis is a major problem in ovarian cancer and correlates with poor prognosis. Osteoprotegerin (OPG) is a secreted factor in malignant ascites and acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL promotes apoptosis in ovarian cancer cells. Ovarian cancer ascites attenuate TRAIL-induced apoptosis raising the possibility that OPG contained in ascites may abrogate the anti-tumor activity of TRAIL.</p> <p>Methods</p> <p>Determination of OPG levels in ascites was measured by ELISA. Effect of OPG on TRAIL-induced cell death was determined by XTT and colony forming assays in ovarian cancer cell lines and primary tumor cells. Apoptosis was assessed by ELISA.</p> <p>Results</p> <p>We found that recombinant OPG and malignant ascites attenuates TRAIL-induced cell death and apoptosis in a dose-dependent manner in ovarian cancer cell lines and primary ovarian tumor cells. OPG is present at high levels in the ascites of patients with ovarian cancer. We found a positive correlation between the levels of OPG in ascites and the ability of the ascites to attenuate TRAIL-induced cell death. The anti-apoptotic effect of ascites was not reversed by co-incubation with an OPG blocking antibody.</p> <p>Conclusions</p> <p>OPG and malignant ascites protect ovarian cancer cells from TRAIL-induced apoptosis. Although malignant ascites contain high levels of OPG, OPG is not a critical component that contributes to ascites-mediated attenuation of TRAIL-induced apoptosis.</p>
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spelling doaj.art-99673aab534b486aa533dd1d7bf8764b2023-01-02T15:15:56ZengBMCJournal of Ovarian Research1757-22152012-11-01513410.1186/1757-2215-5-34Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosisLane DenisMatte IsabelleRancourt ClaudinePiché Alain<p>Abstract</p> <p>Background</p> <p>Resistance to apoptosis is a major problem in ovarian cancer and correlates with poor prognosis. Osteoprotegerin (OPG) is a secreted factor in malignant ascites and acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL promotes apoptosis in ovarian cancer cells. Ovarian cancer ascites attenuate TRAIL-induced apoptosis raising the possibility that OPG contained in ascites may abrogate the anti-tumor activity of TRAIL.</p> <p>Methods</p> <p>Determination of OPG levels in ascites was measured by ELISA. Effect of OPG on TRAIL-induced cell death was determined by XTT and colony forming assays in ovarian cancer cell lines and primary tumor cells. Apoptosis was assessed by ELISA.</p> <p>Results</p> <p>We found that recombinant OPG and malignant ascites attenuates TRAIL-induced cell death and apoptosis in a dose-dependent manner in ovarian cancer cell lines and primary ovarian tumor cells. OPG is present at high levels in the ascites of patients with ovarian cancer. We found a positive correlation between the levels of OPG in ascites and the ability of the ascites to attenuate TRAIL-induced cell death. The anti-apoptotic effect of ascites was not reversed by co-incubation with an OPG blocking antibody.</p> <p>Conclusions</p> <p>OPG and malignant ascites protect ovarian cancer cells from TRAIL-induced apoptosis. Although malignant ascites contain high levels of OPG, OPG is not a critical component that contributes to ascites-mediated attenuation of TRAIL-induced apoptosis.</p>http://www.ovarianresearch.com/content/5/1/34OsteoprotegerinTRAILOvarian carcinomaResistanceAscitesApoptosis
spellingShingle Lane Denis
Matte Isabelle
Rancourt Claudine
Piché Alain
Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
Journal of Ovarian Research
Osteoprotegerin
TRAIL
Ovarian carcinoma
Resistance
Ascites
Apoptosis
title Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
title_full Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
title_fullStr Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
title_full_unstemmed Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
title_short Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis
title_sort osteoprotegerin opg protects ovarian cancer cells from trail induced apoptosis but does not contribute to malignant ascites mediated attenuation of trail induced apoptosis
topic Osteoprotegerin
TRAIL
Ovarian carcinoma
Resistance
Ascites
Apoptosis
url http://www.ovarianresearch.com/content/5/1/34
work_keys_str_mv AT lanedenis osteoprotegerinopgprotectsovariancancercellsfromtrailinducedapoptosisbutdoesnotcontributetomalignantascitesmediatedattenuationoftrailinducedapoptosis
AT matteisabelle osteoprotegerinopgprotectsovariancancercellsfromtrailinducedapoptosisbutdoesnotcontributetomalignantascitesmediatedattenuationoftrailinducedapoptosis
AT rancourtclaudine osteoprotegerinopgprotectsovariancancercellsfromtrailinducedapoptosisbutdoesnotcontributetomalignantascitesmediatedattenuationoftrailinducedapoptosis
AT pichealain osteoprotegerinopgprotectsovariancancercellsfromtrailinducedapoptosisbutdoesnotcontributetomalignantascitesmediatedattenuationoftrailinducedapoptosis