Tumorigenic epithelial clusters are less sensitive to moderate osmotic stresses due to low amounts of junctional E-cadherin

Abstract

AbstractThe migration of tumorigenic epithelial cells is a critical step for metastatic breast cancer progression. Although the role of the extracellular matrix in breast cancer cell migration has been extensively described, the effect of osmotic stress on the migration of tumor breast epithelial cohorts remains unclear. Most of our understanding on the effect of osmotic stresses on cell migration comes from studies at the level of the single cell in isolation and does not take into account cell-cell interactions. Here, we study the impact of moderate osmotic stress on the migration of epithelial clusters composed of either non-tumorigenic or tumorigenic epithelial cells. We observe a decrease in migration distance and speed for non-tumorigenic epithelial cells but not for tumorigenic ones. To explain these differences, we investigate how osmotic stress impacts the mechanical properties of cell clusters and affects cell volumes. After application of osmotic stress renal epithelial cells become stiffer whereas non-tumorigenic and tumorigenic breast epithelial cells do not. In addition, tumorigenic cells are shown to be less sensitive to osmotic stress than non-tumorigenic cells, and this difference is associated with lower levels of E-cadherin expression. Using EGTA treatments, we confirm that the establishment of cell-cell adhesive interactions is a key component of the behavior of epithelial clusters in response to osmotic stress. This study provides evidence on the low sensitivity of tumorigenic epithelial clusters to moderate osmotic stress and highlights the importance of cadherin-based junctions in response to osmotic stress.