The extracellular matrix (ECM) surrounding cancer plays an important role in facilitating cancer progression, metastasis and therapeutic resistance. Pancreatic ductal adenocarcinoma (PDAC) has a unique ECM microenvironment including a dense fibrotic stroma, increased interstitial tissue pressure and mechanical stiffness. Currently, due to the limitations of in-vitro experimental models, few studies have investigated the linkage between chemotherapy outcome and ECM in PDAC.
We have constructed 3-dimensional (3D), physiologically relevant modified Matrigel culture system to co-culture a mouse-derived PDAC organoid and host-matching cancer associated fibroblasts (CAF). Using this engineered novel culture system, we are able to investigate how individual ECM features affects progression and chemotherapy response in PDAC. Illustrated mechanisms will help us identify key regulators of matrix mediated chemo-resistance which can be served as co-targets in clinical solutions.
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