Cancer cells cultured within collagen I hydrogels exhibit an in vivo solid tumor phenotype

Cells cultured within a 3D environment acquire phenotypes and respond to stimuli analogous to in vivo development. This approach can be applied to the study of tumorigenesis in vitro. In this study, collagen I hydrogels were engineered as a platform for in vitro solid tumor development. Cell seeding density, scaffold thickness, and matrix stiffness were varied to characterize the development of a hypoxic environment and necrotic core as well as the expression of a key angiogenic factor in breast cancer cells cultured within collagen I hydrogels. Limitations in oxygen and nutrient diffusion through the collagen I matrix along with competition among cells resulted in necrosis at the core of the tumor constructs and upregulation of both HIF-1a and VEGF-A gene expression. Constructs with a higher cell seeding density and greater thickness exhibited development of a necrotic core more rapidly than constructs where diffusion and competition were not deterrents. The results presented in this study demonstrate the capacity of collagen I hydrogels for facilitating development of tumor constructs that are representative of in vivo solid tumor progression.