Micropatterned topographies reveal measurable differences between cancer and benign cells

Abstract

During metastasis, cancer cells migrate away from the primary tumor-site, encountering different microenvironment topographies that may facilitate or inhibit cancer cell adherence and growth; those relate to sites of invasion and seeding. To evaluate topography effects, poly-lactic-poly-glycolic (PLGA) gels are generated as flat substrates, porous, or with rectangular microchannels of varying widths (5-100 µm) and depths (10/20 µm). The topography effect on time-dependent adherence, proliferation, morphology, alignment and long-term structural development of metastatic breast-cancer and benign cells are evaluated; adherence at short time-scales (3 h) is compared to developed morphologies and multicellular structures (>2 days) indicating function. At short time-scales, both cell types exhibit rounded morphologies, however, while the benign cells tend to cluster the cancer cells preferentially adhered as single cells at high-curvature substrate-sites (e.g. convex pore-edges or channel-edges). At long times, the benign cells develop extensive, tissue-like multicellular sheets spanning across several 10 µm deep channels or filling in single-file 20 µm-deep narrow channels (5-15 µm). Contrastingly, cancer cells mainly attach as single cells to high-curvature channel bottoms, in alignment with narrow channels. Thus, cell responses to topography, specifically their localization and growth in narrow microchannels, may provide a way to distinguish cancer from benign cells, by demonstrating their inherent function.