GSE135515
Tumor Heterogeneity in Metastatic Potential is Indicated by Adhesion Strength
Tumors are heterogeneous and comprised of cells with varying function and ability to disseminate. Despite significant effort, no universal biological marker currently serves as a metric for metastatic potential of solid tumors. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Adhesion strength is heterogeneous even amongst cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups; when cultured under stromal conditions, this adhesion phenotype is stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Subpopulations do not show differences in expression of proteins involved in the focal adhesion complex but do exhibit intrinsic focal adhesion assembly as well as contractile differences that result from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity. Collectively, these differences drive migration in both 2D and 3D migration assays for weakly adherent cells; these differences are maintained over days in culture, suggesting that adhesion strength can serve as a stable marker for migration and metastatic potential within a given tumor population. Moreover, these data suggest that the fraction of weakly adherent cells present within a tumor could act as a novel physical marker for metastatic potential. Overall design: RNA-sequencing profiles of weakly adherent (n = 3) and strongly adherent (n = 2) MDA-MB231 cells isolated via application of shear stress to heterogeneous populations.