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.

Using Biomimetic Scaffold Platform to Detect Growth Factor Induced Changes in Migration Dynamics of Nasopharyngeal Epithelial Cells

“…Hence, NP460 cells with and without TGF-β1 treatment responded differently in the 3D microenvironment. These results are consistent with our previous work that demonstrated different migration behaviors for cells in difference metastasis status when seeded on platforms with different topographies [12]. It is suggested that the topographical structure of the scaffold platforms provided more edges for cell attachment and focal adhesion formation, which favors cell movement [37,38].…”

“…Migration behaviors of cultured cells on 2D platforms with different engineered topographies have been studied extensively [11]. We and others have demonstrated that cell culturing environment can be fabricated with different topographies [12]. Engineered platforms with confined microchannels have been fabricated using polyacrylamide hydrogel with extracellular matrix (ECM) proteins conjugated to control the stiffness and provide biochemical ligands for cell adhesion.…”

“…However, all these studies focused on the lateral movement of cells on different physical confinements. In particular, we have recently shown that the metastatic status of cancer cells could be manifested in the cell migration behaviors on 2D grating structures [12]. These behaviors, including changes in migration speed and directionality, are readily and quickly detectable by low magnification brightfield (BF) microscopy.…”

The Role of Microenvironmental Cues and Mechanical Loading Milieus in Breast Cancer Cell Progression and Metastasis

“…Beyond cell survival, topographic patterning of microscale features can influence cell migration and cytoskeletal composition. MDA-MB-231 cells had the greatest migration and cell speed on the arc pattern compared with grating pattern or flat control surface (Zhou et al, 2017). The uneven pattern of the arcs could create uneven vinculin focal adhesion protein expression within the cell, possibly causing the increased migration.…”

Controlled Scaffold Platform Designs on Nasopharyngeal Carcinoma Cell Separation

“…It is a primary cellular process that occurs continuously, sometimes leading to the progression of pathogenic diseases [22]. Previous studies reported cell migration behaviors on two-dimensional (2D) platforms with various engineered topographies [23][24][25][26][27][28][29][30]. However, 2D models do not accurately represent the microenvironment of tumors in vivo.…”