Superfund Research Program
Vascular Mechanisms of PCB-Induced Brain Metastases
Project Summary (2005-2008)
Polychlorinated biphenyls (PCBs) are industrial chemicals mass produced and sold on a large scale in the
- alterations of cellular redox status and overexpression of prometastatic/proinflammatory genes;
- overexpression of matrix metalloproteinases (MMPs); and
- alterations of expression of junctional proteins and disturbances of endothelial barrier function.
This research combines elements of clinical approaches (brain metastases), environmental toxicology with molecular and vascular biology. In addition, it is based on a variety of model systems, such as cultures of endothelial cells, Transwetl systems to study permeability across the model of brain endothelium, and animal studies. The long-term goals of this project are to determine the mechanisms which are responsible for PCB-induced injury to brain endothelial cells, disruption of the BBB and the development of brain metastases. Data arising from this project will be critical for a better understanding of the molecular mechanisms of brain metastasis formation. In a broader aspect, this research will contribute to better knowledge on how air pollution contributes to cancer biology and the development of metastases.