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

• 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(scid)/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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Animals

Apoptosis

Biomarkers, Tumor

Breast Neoplasms

Cartilage Oligomeric Matrix Protein

Cell Adhesion

Cell Line

Cell Membrane

Cell Movement

Cell Transformation, Neoplastic

Disease Models, Animal

Endoplasmic Reticulum

Endoplasmic Reticulum Stress

Female

Gene Expression

Gene Expression Profiling

Heterografts

Humans

Immunohistochemistry

Matrix Metalloproteinase 9

Mice, SCID

Neoplasm Metastasis

Oxidative Phosphorylation

Prognosis

Proportional Hazards Models

Recurrence

Journal Article

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)