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

Englund, Emelie LU ; Canesin, Giacomo LU ; Papadakos, Konstantinos S. LU ; Vishnu, Neelanjan LU ; Persson, Emma ; Reitsma, Bart LU ; Anand, Aseem LU ; Jacobsson, Laila LU ; Helczynski, Leszek LU and Mulder, Hindrik LU , et al. (2017) In Oncotarget 8(58). p.98298-98311
Abstract

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... (More)

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 Ca2+ signalling by preventing Ca2+ 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 Ca2+ homeostasis of cancer cells.

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@article{34cfc4b8-c007-4bcb-bfc6-38e937080d78,
  abstract     = {<p>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<sup>2+</sup> signalling by preventing Ca<sup>2+</sup> 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<sup>2+</sup> homeostasis of cancer cells.</p>},
  author       = {Englund, Emelie and Canesin, Giacomo and Papadakos, Konstantinos S. and Vishnu, Neelanjan and Persson, Emma and Reitsma, Bart and Anand, Aseem and Jacobsson, Laila and Helczynski, Leszek and Mulder, Hindrik and Bjartell, Anders and Blom, Anna M.},
  issn         = {1949-2553},
  language     = {eng},
  number       = {58},
  pages        = {98298--98311},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis},
  url          = {http://dx.doi.org/10.18632/oncotarget.21176},
  doi          = {10.18632/oncotarget.21176},
  volume       = {8},
  year         = {2017},
}