Tumor metastasis after hyperoxic injury and repair of the pulmonary endothelium.
Pulmonary metastasis is a common event. The studies described here were done to test the hypothesis that there is a relationship between endothelial injury and the localization and metastasis of circulating tumor cells. Mice were exposed for periods of up to 4 days to an atmosphere of 90% oxygen; some were allowed to recover in room air for 3 or 14 days. Air-exposed animals served as controls. Endothelial injury, demonstrated morphologically and quantitated by measuring protein levels in bronchoalveolar lavage fluid, increased from 2 to 4 days exposure when injury was maximal. Metastatic events increased in frequency concurrently. When radiolabeled syngeneic fibrosarcoma cells were injected, a 5-fold increase in localization at 24 hours was seen in the 3-day exposed group and a 36-fold increase was found in the 4-day group. Tumor cells were found by electron microscopy at sites of denuded endothelial basement membrane, often associated with small platelet-fibrin thrombi and sometimes, after 4-day exposure, with sequestered neutrophils. The subsequent development of metastatic nodules in the lung and the percentage of lung occupied by tumor were also maximal in the 4-day group. Increased metastasis and endothelial injury were also seen in mice returned to air for 3 days, but by 14 days the endothelium was normal and metastases were at control levels. The results demonstrate a relationship between the degree of pulmonary endothelial damage produced by hyperoxia and the extent of metastatic tumor growth.
D000818:Animals; D001345:Autoradiography; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D005354:Fibrosarcoma / Q000556:secondary; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010100:Oxygen / Q000633:toxicity*
D010100:Oxygen