Speaker
Description
Pancreatic cancer precursor lesions (PanINs and IPMNs) generate pronounced ductal deformations, arising from reciprocal interactions between epithelial mechanics, basement membrane integrity, and stromal remodeling. Yet the dynamic feedback loops governing this structural evolution remain poorly characterized. We present a multiscale mathematical modeling framework that couples ductal epithelial cells, the basement membrane, and cancer associated fibroblasts (CAFs). The model integrates mechanistic rules for cell-matrix adhesion, epithelial mechanical responses, and CAF driven matrix remodeling to characterize how specific parameter combinations generate the ductal morphologies observed in precursor lesions. Simulations reveal how variations in epithelial stiffness, basement membrane degradation kinetics, and CAF remodeling rates produce canonical deformation modes consistent with histological sections from resected human pancreas tissues. Current work extends the framework to enable predictive exploration of lesion progression, identifying parameter regimes that shift lesions toward increased morphological irregularity and potential invasiveness. This modeling approach provides a mathematically rigorous platform for quantifying multicellular interactions and uncovering mechanistic drivers of early pancreatic neoplastic evolution.
