A 3D model to evaluate cell chemotaxis within a heterogenic tumor microenvironment

Abstract

As studies continue to bring forward data on both the complexity and heterogeneity behind the tumor microenvironment, new strategies to understand and unravel the cellular interactions that regulate tumor progression and tumor cell invasion are required. Here, we present a novel and tailorable 4-well 3D culture chamber design capable of studying chemotaxis between several distinct cell types and a cancer cell population of interest. The use of a type I collagen hydrogel as the 3D substrate allowed for a differential molecule diffusion, in which rate of diffusion was associated with molecular weight. When culturing different human stromal cells (hASCs, hDMECs and hDFbs) in the outer wells while keeping VMM15 melanoma cells within the central well it was observed that hASCs and hDFbs presented directional migration throughout the collagen matrix towards the tumor cells. Further analysis revealed a higher area of migration present in the hDFbs when compared to the hASCs, supporting the potential of this system to study the recruitment of supporting cells by cancer cells and how this may impact tumor invasion.