Examining Endothelial Cell Contractility During Tumor Cell-Induced Barrier Disruption

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Author:
Khouri, Joelle Najla
Area of Honors:
Chemical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Esther Winter Gomez, Thesis Supervisor
  • Michael John Janik, Honors Advisor
Keywords:
  • endothelial cells
  • melanoma
  • contractility
  • focal adhesions
  • actin
  • cytoskeleton
  • traction force
Abstract:
Melanoma is the most serious type of skin cancer due to its high metastatic potential. During metastasis, cancer cells disrupt the endothelial barrier twice: once to enter the bloodstream and once to leave it. The exact mechanisms through which tumor cells interact with endothelial cells to induce breakdown of endothelial cell-cell junctions, however, is unknown. This thesis investigates the effect of metastatic and non-metastatic melanoma cells on the contractility of endothelial cells, captured through analysis of actin cytoskeleton organization, focal adhesion properties, and cell forces. The results indicate that metastatic melanoma cells interact with the endothelium differently than non-metastatic melanoma cells to increase endothelial cell contractility. These results were manifested in increased F-actin fiber alignment and increased focal adhesion number and size in endothelial cells in contact with metastatic melanoma cells. These features may contribute to disruption of endothelial cell-cell junctions and increased permeability of the endothelium.