Research Papers:
Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
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Abstract
Emelie Englund1, Giacomo Canesin2,*, Konstantinos S. Papadakos1,*, Neelanjan Vishnu3, Emma Persson1, Bart Reitsma1, Aseem Anand2, Laila Jacobsson3, Leszek Helczynski2, Hindrik Mulder3, Anders Bjartell2 and Anna M. Blom1
1Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Malmö, Sweden
2Department of Translational Medicine, Division of Urological Cancers, Lund University, Malmö, Sweden
3Department of Clinical Sciences Malmö, Unit of Molecular Metabolism, Lund University, Malmö, Sweden
*These authors have contributed equally to this work
Correspondence to:
Anna M. Blom, email: [email protected]
Keywords: prostate cancer; cancer progression; apoptosis; metabolism; Ca2+ signalling
Received: May 31, 2017 Accepted: August 27, 2017 Published: September 21, 2017
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 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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