BioProject

Cartilage Oligomeric Matrix Protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. More...

Cartilage Oligomeric Matrix Protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Publicly available mRNA expression array data indicated that COMP is overexpressed in breast cancer tissue. Tissue microarrays derived from two cohorts of patients with breast cancer (n = 122 and n = 498) were immunostained, which revealed varying amounts of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and faster recurrence (metastases). Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdcscid/Rj) mice. Tumors expressing COMP grew to significantly larger volumes and had increased metastasis as compared to control, mock transfected, tumors. In vitro experiments confirmed that COMP expressing cells were more invasive, which was in part related to an upregulation of metalloprotease-9. Further, microarray analyses of gene expression in tumors formed in vivo showed that expression of COMP was protective against endoplasmatic reticulum stress. This observation was confirmed in vitro since COMP expressing cells showed better survival than mock when treated with brefeldin, which leads to accumulation of proteins in endoplasmatic reticulum. The mRNA pathway analyses also implicated a metabolic switch leading to a more severe Warbug effect, which was confirmed in vitro by measurement of cell respiration and lactate production. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by several novel molecular mechanisms. Overall design: Tumours from seven wildtype and seven COMP-overexpressing arrays were analysed using Illumina whole genome mouse arrays. Less...