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Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis
Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promotin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302663/ https://www.ncbi.nlm.nih.gov/pubmed/24976340 http://dx.doi.org/10.1002/cam4.277 |
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author | Weichhaus, Michael Segaran, Prabu Renaud, Ashleigh Geerts, Dirk Connelly, Linda |
author_facet | Weichhaus, Michael Segaran, Prabu Renaud, Ashleigh Geerts, Dirk Connelly, Linda |
author_sort | Weichhaus, Michael |
collection | PubMed |
description | Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells. |
format | Online Article Text |
id | pubmed-4302663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43026632015-01-22 Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis Weichhaus, Michael Segaran, Prabu Renaud, Ashleigh Geerts, Dirk Connelly, Linda Cancer Med Cancer Biology Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells. Blackwell Publishing Ltd 2014-10 2014-06-28 /pmc/articles/PMC4302663/ /pubmed/24976340 http://dx.doi.org/10.1002/cam4.277 Text en © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Weichhaus, Michael Segaran, Prabu Renaud, Ashleigh Geerts, Dirk Connelly, Linda Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title | Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title_full | Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title_fullStr | Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title_full_unstemmed | Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title_short | Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
title_sort | osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302663/ https://www.ncbi.nlm.nih.gov/pubmed/24976340 http://dx.doi.org/10.1002/cam4.277 |
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