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Cell-cell interactions during transendothelial migration of tumor cells
1Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Microscopy Research and Technique
|December 5, 1998
Summary
Cancer cells migrate through blood vessels by interacting with endothelial cells. This study reveals specific cadherin molecules facilitate tumor cell transmigration and endothelial cell junction dynamics during metastasis.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Cancer metastasis involves tumor cells migrating through endothelial barriers.
- Tumor cell transmigration requires interaction with endothelial cell junctions, rich in VE-cadherin and PECAM-1.
Purpose of the Study:
- To investigate the dynamic interactions between melanoma cells and endothelial cells during transmigration.
- To identify the roles of specific cell adhesion molecules, particularly cadherins, in this process.
Main Methods:
- Utilized an in vitro model of melanoma cells on endothelial cell monolayers cultured on Matrigel.
- Observed cytoskeletal reorganization and cell shape changes using microscopy.
- Analyzed the redistribution and expression of VE-cadherin, PECAM-1, pan-cadherin, and N-cadherin.
Main Results:
- Melanoma cell transmigration involves membrane blebbing and pseudopod extension.
- Endothelial cell junctions transiently dissolve, with redistribution of VE-cadherin and PECAM-1.
- N-cadherin is concentrated at the leading edges of endothelial cell processes that reform the monolayer.
- Pan-cadherin is present in heterotypic contacts between tumor and endothelial cells.
Conclusions:
- Endothelial cells actively participate in tumor cell transmigration.
- Specific cadherin family members play distinct roles in regulating endothelial barrier permeability and tumor cell invasion.
- Understanding these interactions could reveal new therapeutic targets for inhibiting metastasis.