Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer

Abstract

Cartilage oligomeric matrix protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Tissue microarrays derived from two cohorts of patients with breast cancer (n=122 and n=498) were immunostained, revealing varying expression 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 decreased recurrence-free survival. Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdc/Rj) mice. Tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control, mock-transfected, tumors. In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of matrix metalloprotease-9. Furthermore, microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. This observation was confirmed in vitro as COMP-expressing cells showed better survival as well as a higher rate of protein synthesis when treated with brefeldin A, compared with control cells. Further, COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect. Thus, in vitro measurement of cell respiration indicated decreased mitochondrial metabolism. In conclusion, COMP is a novel biomarker in breast cancer, which contributes 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.

The role of complement inhibitors beyond controlling inflammation

“…Indeed, immunohistochemical staining of tissue biopsies from two independent cohorts has shown COMP in fibroblasts and ECM in breast cancer tissue. More surprisingly, COMP was also frequently expressed by epithelial breast tumour cells and such expression strongly correlated with poor patient survival and the presence of metastases independently of other markers . This finding was confirmed in a mouse xenograft model in which human breast cancer MDA‐MB‐231 cells expressing COMP formed much larger tumours producing more frequent metastases than mock‐transfected cells.…”

Serum protein profiling in diffuse large B‐cell lymphoma

“…MMRN2 is an ECM glycoprotein involved in cell adhesion that has been previously identified as a biomarker for ovarian, breast, and lung cancers . COMP is a soluble pentameric protein involved in collagen organization that has been implicated as a biomarker for advanced breast and prostate cancers .…”

Bioinformatics Analysis to Screen the Key Prognostic Genes in Tumor Microenvironment of Bladder Cancer

“…Furthermore, high COMP expression plays a crucial role in regulating cellular metabolism by blocking intracellular Ca 2+ signaling and thus blocking the apoptosis process of the cells [39]. Previous studies have shown that COMP expression in breast cancer cells is significantly associated with poor prognosis [40]. Moreover, COMP expression was also found in colorectal, gastric, lung, ovarian, and pancreatic cancers as shown in the analysis of expression data using the Oncomine database [38].…”