Physical contact with breast cancer weakens endothelial cell chirality.

Cells have been recently discovered processing a phenotype-specific chirality which can be seen as directional cell alignment, rotation, or migration. Endothelial cells (ECs) exhibit a strong right bias (or clockwise chirality) under normal conditions. Enervating this chirality impairs EC junction formation and leads to significant leakage of the blood vessels. Malfunction of endothelial barrier induced by malignant tumor cell (TC) facilitates metastasis; however, the role of EC chirality during its crosstalk with TCs is still poorly understood. Using a Transwell model, we evaluated the chirality of human umbilical vein endothelial cells (HUVECs) on a ring-shaped micropattern with direct or indirect co-culture of TCs. Our data show a significant loss, or partial reversal of EC chirality when MCF10A-HRAS or MCF10A-HER2 cells were directly introduced to EC populations, while indirect co-culture with either type of TCs only caused a minor decrease in EC chirality. Furthermore, we characterized the bias of each EC on the micropattern using a cell organelle-based labeling and image analysis. We found the ECs in direct contact with TCs trend to reverse their bias, while the "spaced ones" do not. Together, our results suggest direct physical contact with malignant TCs could cause the EC chirality weakening, which potentially compromises the overall endothelial integrity and contributes to cancer spread.