Mechanical interactions in 3D tumor/fibroblast co-culture models of pancreatic cancer

Studies have shown that mechanical interactions between tumor cells and stromal components in the tumor microenvironment impact disease progression and therapeutic response. Tumors of the pancreas are associated with an abundance of stiff fibrous stroma impacting growth and drug delivery. Here we use time lapse imaging to study physical interactions between pancreatic ductal adenocarcinoma (PDAC) cells and stromal fibroblasts grown in 3D culture on laminin rich extracellular matrix (ECM). PDAC cells overlaid on ECM form compact multicellular 3D nodules. When fibroblasts are introduced there is a profound change in growth behavior culminating in the formation of large connected structures. We describe quantitative analysis of this behavior using particle image velocimetry. We contrast stromal interactions of PANC1 PDAC cells and a previously established associated drug-resistant sub-line, showing that drug naïve co-cultures and drug resistant co-cultures are quantifiably different in both distribution of per-frame average magnitude over time, as well as final spatial distribution of spheroids in the co-cultures. Going forward, the methodology for cultivating fibrotic PDAC tumors in vitro may comprise a useful platform for screening drug delivery approaches for this lethal disease.