Breast Cancer Cells Reduce the Stiffness of Endothelial Cells

Abstract

Metastasis formation is a key component of malignant tumor progression. The capability to metastasize depends on the cancer cell¯s potential to invade connective tissue, adhere, and potentially transmigrate through the endothelium. How invasive cancer cells diminished the endothelial barrier function is still elusive. We hypothesize that some invasive cancer cells can decrease the endothelial barrier function through reduction of the endothelial cell stiffness. Using cell invasion assay in dense 3D collagen matrices, we observed that MDA-MB-231 breast cancer cells invade collagen matrices, and that their invasiveness is significantly increased in the presence of an endothelial cell monolayer. Using microrheology magnetic tweezer measurements, we investigated whether invasive breast cancer cells alter endothelial cell¯s mechanical properties. Indeed, we found that these invasive cancer cells reduce the stiffness of co-cultured microvascular endothelial cells compared to mono-cultured endothelial cells. The reduction of cellular stiffness in endothelial cells may explain the break down of the barrier function of endothelial cells that was induced by breast cancer cells. In summary, the mechanical measurements of cells help to identify molecules and signal transduction pathways that control biological processes such as cell invasiveness and metastasis. These measurements may emerge as a powerful tool to analyze whether cancer cells may be able to break down the endothelial cell barrier by altering endothelial cell¯s mechanical properties.