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Intratumoral phenotypic heterogeneity as an encourager of cancer invasion.

We present a novel in vitro breast tumor model to mimic intratumoral phenotypic heterogeneity based on a microfluidic system incorporating ECM scaffolds capable of providing a physiologically relevant tumor microenvironment. To study the regulation of invasive potentials by intratumoral subpopulation conditions, we developed heterogeneous cancer cell subpopulations by co-culturing two breast cancer cell types with distinct phenotypes, specifically, highly invasive and epithelial-like cancer cells. Our results indicate that intratumoral phenotypic heterogeneity acts as an encourager of cancer cell invasion through a 3D matrix depending on the neighboring ECM, with highly invasive cancer cells acting as the 'leader' and epithelial-like cancer cells as the 'follower', therefore enhancing the metastatic potential.