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FAP Activity Is Reflected by a Specific Fragment of Type III Collagen
June 17, 2024
The activity of fibroblast activation protein (FAP) is reflected by a specific fragment of type III collagen that can be serologically assessed and serve as a non-invasive biomarker
Introduction
Non-small cell lung cancers (NSCLC) are associated with both inflammatory and fibrotic tumor microenvironments (TME). The inflammatory component involves an influx of macrophages, which release matrix metalloproteinases (MMPs) that cleave extracellular matrix proteins, including type III collagen, leading to the release of the C3M fragment into circulation. In parallel, tumor fibrosis is marked by the accumulation of fibroblasts and high expression of Fibroblast Activation Protein (FAP), which is typically low or absent in benign tissue. FAP possesses unique proteolytic activity and has been shown to cleave various ECM proteins, including collagens.
Based on this, we hypothesized that FAP-mediated cleavage of type III collagen would generate a distinct fragment, C3F, that could enter the circulation and serve as a potential marker of FAP activity within the TME.
Poster
Conclusion
FAP activity can be assessed by targeting a FAP-cleaved fragment of type III collagen, C3F and function as a non-invasive biomarker for patients with NSCLC. By showing that this fragment differs from the MMP-generated fragment C3M, this study supports the notion that different biological processes are reflected in the proteolytic degradation of the ECM and can be reflected by specific circulating protein fragments.
