Substrates with patterned topography reveal metastasis of human cancer cells

Abstract

In this study, we aimed at studying the effects of engineered and patterned substrates on the migration characteristics of mammalian cancer cell lines. On the shallow topographical patterns, cells from different histological origins showed different migration speed and directionality. We also observed that cells from the same origin showed distinctive behaviour, suggesting these substrate topographies could distinguish cancer subtypes. To eliminate the influence of genetic background, we examined two isogenic subpopulations of ovarian cancer cell lines for their different metastatic activities. While these cell lines showed indistinguishable migration characteristics on a flat substrate, their motilities on the patterned substrates were highly different, suggesting that cancer cells’ motilities on these substrates varied in a metastasis-dependent manner. While cells with different metastatic activities showed similar morphology and focal adhesion distribution on flat surface, vinculin aggregated into single cytoplasmic foci in metastatic cells cultured on the engineered substrates. This implies that the topographical patterns on the substrates induced vinculin redistribution in cancer cells with a higher invasive activity. The fabricated platforms with topographical patterns offer a novel in vitro technique for metastasis assessment. Moreover, such platforms could potentially provide the opportunity to sort cells in different metastatic states using advanced pattern designs and features.