Novel hydrogel-based cancer-on-a-chip models for growth of 3D multi-cellular structures and investigation of early angiogenesis in pancreatic ductal adenocarcinoma

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Cancer-on-a-chip models have enormous potential for the study of tumour development events. Here, we investigated hydrogels of egg white (EW) and gelatin for growth of 3D multi-cellular structures and investigation of early angiogenesis inside microfluidic devices. We focused on pancreatic ductal adenocarcinoma (PDAC), a devastating gastrointestinal malignancy. EW/gelatin hydrogels were stiffer and showed porous globular structures compared to the fibrous network of collagen I molecules. PANC-1 cells preferentially formed significantly larger spheroids in collagen I than in EW/gelatin hydrogels, whilst cell aggregates in the shape of grape-like clusters were significantly larger and more abundant in EW/gelatin. Cells inside the aggregates showed active cell unions, secreted matrix, and formed active unions with the surrounding EW/gelatin hydrogel. Early stages of PDAC were recreated by co-culture of two different microenvironments, one for PANC-1 and another one for fibroblasts, for investigating the secretion of soluble angiogenic factors, which depended on the role of each factor in the angiogenic and tumorigenic processes. Overall, cancer cell proliferation and establishment of a tumour vasculature were favoured. This study demonstrates the importance of the microenvironment in tumour cells behaviour as well as the complex interplay between the different cells present in PDAC to establish a tumoural vasculature.

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