Growth and Spread of Breast Cancer Linked to Tumor Cells' Expression of a Cartilage Protein

Investigators at Lund University (Malmö, Sweden) using tissue microarrays derived from two cohorts of patients with breast cancer found that the protein COMP (cartilage oligomeric matrix protein), a soluble pentameric protein expressed in cartilage and involved in collagen organization, was expressed to a varying degree in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and decreased recurrence-free survival. Normal breast tissue did not express detectable levels of COMP.

The investigators injected MDA-MB-231breast cancer cells that stably expressed COMP into the mammary fat pads of SCID (CB-17/Icr-Prkdcscid/Rj) mice. They reported in the April 11, 2016, online edition of the journal Oncogene that tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control tumors that did not express the protein.

In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of the enzyme matrix metalloprotease-9. Microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. Furthermore, in vitro measurement of cell respiration indicated that COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect, in which they produced energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria as in most normal cells.

Based on these results, the investigators concluded that COMP was a novel biomarker in breast cancer, which contributed to the severity of the disease by metabolic switching and increasing invasiveness and tumor cell viability, leading to reduced survival in animal models and human patients.

"We saw a clear association between high levels of COMP and a worse breast cancer prognosis. With more research, COMP has the potential of becoming an indicator of aggressive breast cancer, and thereby providing early and valuable information before deciding on an appropriate treatment," said senior author Dr. Anna Blom, professor of protein chemistry at Lund University.

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