THE EFFECTS OF THE TUMOR MICROENVIRONMENT ON ENDOTHELIAL CELLULAR ADHESION MOLECULE EXPRESSION

Open Access
Author:
Goodrich, Christopher James
Area of Honors:
Bioengineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Cheng Dong, Thesis Supervisor
  • William O Hancock, Honors Advisor
  • Peter J Butler, Faculty Reader
Keywords:
  • cancer
  • metastasis
  • adhesion
  • ICAM-1
Abstract:
The goal of this work is to evaluate the how tumor cells interact with and, in effect, change endothelial cells. Through the development of a contact coculture assay, tumor cells and endothelial cells could be cultured separately while still allowing for some direct cell-to-cell contact. This allowed for the measurement of endothelial cellular adhesion molecule expression level changes due to direct cell-to-cell contact with melanoma cells. It was found that direct cell contact resulted in significant increases in ICAM-1 expression levels on HUVEC following a 4 hour coculture. In comparison, HUVEC exposed to only tumor-secreted cytokines did not have the same increase in ICAM-1. Evaluation of cytokine levels following coculture showed increases in IL-8, IL-6, and Gro-á following coculture, though not enough to induce ICAM-1 expression. The results point to cell-to-cell contact as the trigger for increased ICAM-1 expression. Through cross-linking of certain other cellular adhesion molecules on endothelial cells, it was determined that increases in ICAM-1 expression can occur as a result of receptor-ligand interactions between cell types, most likely involving P-Selectin and E-Selectin. Further research needs to be done to determine the specific mechanism of how these interactions specifically cause ICAM-1 upregulation. However, the establishment of cell contact as the cause of rapid ICAM-1 upregulation provides a substantial foundation for further research into the mechanics of melanoma metastasis, and down the line, potential treatment methods.