Biomarker Portfolio

During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragments, so-called neo-epitopes.

Mass spectrometric analysis of cleaved type VI collagen revealed a large number of protease-generated neo-epitopes. A fragment unique to type VI collagen generated by MMP-2 and MMP-9 was selected for ELISA development. The CO6-MMP assay was evaluated in two rat models of liver fibrosis. This novel ELISA is the first assay enabling assessment of MMP degraded type VI collagen, allowing quantification of type VI collagen degradation, which would be relevant for different pathologies. The marker was highly associated with liver fibrosis in two liver fibrosis animal models, suggesting type VI turnover to be a central player in fibrogenesis.

Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activated fibroblast and altered proteolytic degradation by matrix metalloproteases (MMPs). Consequently, pathology-specific COL6 fragments are released to the circulation. MMP-generated COL6 fragments were elevated in serum from cancer patients compared to controls and had promising diagnostic accuracy. This supports that MMP-mediated COL6 remodeling is important in tumorigenesis and indicate cancer biomarker potential of quantifying COL-6 fragments in serum. 

• A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders
• Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
• Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis
• Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study
• Matrix Metalloprotease Generated Fragments of Type VI Collagen Have Serum Biomarker Potential in Cancer - A Proof of Concept Study
• MMP mediated degradation of type VI collagen is highly associated with liver fibrosis
• Progressive alcohol-related liver fibrosis is characterised by imbalanced collagen formation and degradation
• Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men