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Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis

Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prosta...

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Autores principales: Englund, Emelie, Canesin, Giacomo, Papadakos, Konstantinos S., Vishnu, Neelanjan, Persson, Emma, Reitsma, Bart, Anand, Aseem, Jacobsson, Laila, Helczynski, Leszek, Mulder, Hindrik, Bjartell, Anders, Blom, Anna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716730/
https://www.ncbi.nlm.nih.gov/pubmed/29228690
http://dx.doi.org/10.18632/oncotarget.21176
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author Englund, Emelie
Canesin, Giacomo
Papadakos, Konstantinos S.
Vishnu, Neelanjan
Persson, Emma
Reitsma, Bart
Anand, Aseem
Jacobsson, Laila
Helczynski, Leszek
Mulder, Hindrik
Bjartell, Anders
Blom, Anna M.
author_facet Englund, Emelie
Canesin, Giacomo
Papadakos, Konstantinos S.
Vishnu, Neelanjan
Persson, Emma
Reitsma, Bart
Anand, Aseem
Jacobsson, Laila
Helczynski, Leszek
Mulder, Hindrik
Bjartell, Anders
Blom, Anna M.
author_sort Englund, Emelie
collection PubMed
description Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells. Purified COMP bound to and enhanced the invasion of DU145 cells in vitro in an integrin-dependent manner. In addition, intracellular COMP expression interfered with cellular metabolism by causing a decreased level of oxidative phosphorylation with a concurrent upregulation of lactate production (Warburg effect). Further, expression of COMP protected cells from induction of apoptosis via several pathways. The effect of COMP on metabolism and apoptosis induction was dependent on the ability of COMP to disrupt intracellular Ca(2+) signalling by preventing Ca(2+) release from the endoplasmic reticulum. In conclusion, COMP is a potent driver of the progression of prostate cancer, acting in an anti-apoptotic fashion by interfering with the Ca(2+) homeostasis of cancer cells.
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spelling pubmed-57167302017-12-08 Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis Englund, Emelie Canesin, Giacomo Papadakos, Konstantinos S. Vishnu, Neelanjan Persson, Emma Reitsma, Bart Anand, Aseem Jacobsson, Laila Helczynski, Leszek Mulder, Hindrik Bjartell, Anders Blom, Anna M. Oncotarget Research Paper Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells. Purified COMP bound to and enhanced the invasion of DU145 cells in vitro in an integrin-dependent manner. In addition, intracellular COMP expression interfered with cellular metabolism by causing a decreased level of oxidative phosphorylation with a concurrent upregulation of lactate production (Warburg effect). Further, expression of COMP protected cells from induction of apoptosis via several pathways. The effect of COMP on metabolism and apoptosis induction was dependent on the ability of COMP to disrupt intracellular Ca(2+) signalling by preventing Ca(2+) release from the endoplasmic reticulum. In conclusion, COMP is a potent driver of the progression of prostate cancer, acting in an anti-apoptotic fashion by interfering with the Ca(2+) homeostasis of cancer cells. Impact Journals LLC 2017-09-21 /pmc/articles/PMC5716730/ /pubmed/29228690 http://dx.doi.org/10.18632/oncotarget.21176 Text en Copyright: © 2017 Englund et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Englund, Emelie
Canesin, Giacomo
Papadakos, Konstantinos S.
Vishnu, Neelanjan
Persson, Emma
Reitsma, Bart
Anand, Aseem
Jacobsson, Laila
Helczynski, Leszek
Mulder, Hindrik
Bjartell, Anders
Blom, Anna M.
Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title_full Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title_fullStr Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title_full_unstemmed Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title_short Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
title_sort cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716730/
https://www.ncbi.nlm.nih.gov/pubmed/29228690
http://dx.doi.org/10.18632/oncotarget.21176
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