Summary
Cancer cells frequently disseminate via the bloodstream where the endothelium acts as a barrier between the circulating tumor cells and the extravascular tissue. Free radicals generated by environmental factors or host cells can cause endothelial cell injury and we have postulated that such injury could promote the metastasis of intravascular tumor cells. In mice and rats endothelial damage was induced by intravenous cobra venom factor which activates circulating leukocytes. Endothelial cell damage was demonstrated by morphology and by altered vasopermeability. When 125IUdr-labelled cancer cells were injected intravenously, during periods of maximal endothelial cell injury there was a 3 fold increase in retention of these cells in the lung, 24 hours later. After 14 days there was a 3–20 fold increase in the number of metastatic tumors in CoF-treated animals. In both rats and mice, tumor cell localization was reduced 70–80% by pretreatment of the animals with catalase. In mice, endothelial injury induced by bleomycin (120 mg/kg) or by exposure to 90% oxygen for 2–4 days also significantly increased the metastasis of circulating cancer cells. Studies in vitro have demonstrated that rat Walker 256 cancer cells or host cells, when activated with the chemotactic peptide N-fMLP, generate oxygen-derived free radicals and can damage cultured endothelium. When fMLP-activated W256 cells were incubated with 3H-2-deoxyglucose-labelled endothelial cell monolayers, there was a 27% increase in the specific release of isotope within 90 minutes. Damage correlated with tumor cell-induced chemiluminescence and was inhibited by catalase. We conclude that free radical-mediated damage to the microvasculature facilitates the metastasis of circulating cancer cells.
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Shaughnessy, S.G., Warner, D., Buchanan, M.R., Lafrenie, R., Orr, F.W. (1991). The Effects of Oxygen Radical — Mediated Pulmonary Endothelial Damage on Cancer Metastasis. In: Honn, K.V., Marnett, L.J., Nigam, S., Walden, T.L. (eds) Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury. Developments in Oncology, vol 67. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3874-5_22
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DOI: https://doi.org/10.1007/978-1-4615-3874-5_22
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