(918.8) Physical contact with breast cancer weakens endothelial cell chirality

Poster Board Number: D79

Benson Hang (University of Michigan - Dearborn), Hanan Mohammed (University of Michigan - Dearborn), Leo Wan (Rensselaer Polytechnic Institute, Rensselaer Polytechnic Institute, Rensselaer Polytechnic Institute), Jie Fan (University of Michigan - Dearborn)

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.

Support or Funding Information

Supported by the Startup Grant (to JF) from the Department of Natural Sciences, University of Michigan-Dearborn; Research Initiation amp; Development Grant (to JF) from the Office of Research, University of Michigan-Dearborn; Summer Undergraduate Research Experience Program (to BH) from the Office of Research and Sponsored Programs, University of Michigan-Dearborn; and Pilot program for undergraduate student researcher (to BH) from College of Arts, Sciences, and Letters, University of Michigan-Dearborn.

lt;pgt;Supported by the Startup Grant (to JF) from the Department of Natural Sciences, University of Michigan-Dearborn; Research Initiation amp;amp; Development Grant (to JF) from the Office of Research, University of Michigan-Dearborn; Summer Undergraduate Research Experience Program (to BH) from the Office of Research and Sponsored Programs, University of Michigan-Dearborn; and Pilot program for undergraduate student researcher (to BH) from College of Arts, Sciences, and Letters, University of Michigan-Dearborn.lt;/pgt;