Capturing the Heterogeneity of the PDAC Tumor Microenvironment: Novel Triple Co-Culture Spheroids for Drug Screening and Angiogenic Evaluation

This study explores the complexity of pancreatic ductal adenocarcinoma (PDAC) and its tumor microenvironment (TME), which plays a crucial role in treatment resistance. To better replicate this environment, the researchers developed triple co-culture spheroid models incorporating cancer cell lines (MiaPaCa-2 and BxPC-3), pancreatic stellate cell lines (RLT-PSC and hPSC21), and the endothelial cell line HMEC-1.

These spheroids were evaluated through various assays to assess growth, cell viability, and response to therapeutic agents. A key aspect of the study was the evaluation of endothelial cell monolayers using the IKOSA Network Formation Assay, which provided essential parameters for quantifying angiogenesis: the number of loops, total tube length, total covered area of the vessels, and the number of branching points, offering insights into blood vessel formation.

The study demonstrated that these triple co-culture spheroids closely mimic the PDAC microenvironment and revealed significant variations in drug responses based on cellular composition, density, and spatial arrangement. Unlike other models, this approach effectively captures the complexity and heterogeneity of PDAC using a simple, inexpensive, and easily reproducible method while ensuring that each cell population is present in clinically relevant numbers. The researchers highlighted the value of these spheroids for high-throughput drug screening and angiogenesis evaluation but emphasized that their applications extend beyond these areas.