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TGFBI Is the Local Mediator of Pathological TGF-β Activity in Pancreatic Fibroblasts
September 13, 2024
Stroma-derived βigH3 (TGFBI) is the local mediator of pathological TGF-β activity in pancreatic fibroblasts and a target to treat in cancer patients with high fibrotic activity
Introduction
The pro-peptide of type III collagen (nordicPRO-C3™) is a circulating prognostic biomarker that can identify cancer patients with active fibrosis. Consequently, modifiers of nordicPRO-C3™ expression are potential anti-fibrotic targets for cancer. The aim was to identify genetic variants associated with circulating nordicPRO-C3™ levels and explore the relevance as pharmacological targets for treatment of fibrotic cancers.
Poster
Conclusion
An association between BigH3 and nordicPRO-C3™ was found by GWAS, in vitro, and in patients with PDAC: TGF-β induce BigH3, which subsequently activate fibroblasts to become fibrotic, resulting in elevated levels of nordicPRO-C3™, which in turn can be modulated by an anti-BigH3 antibody. This highlights the potential for treatment of tumor fibrosis by inhibiting BIGH3 in cancer patients with elevated nordicPRO-C3™ levels.
