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 accuracy. This supports that MMP-mediated COL6 remodeling is important in tumorigenesis and indicate cancer biomarker potential of quantifying COL-6 fragments in serum.
