Drug-induced endothelial injury potentiates lung colonization in a murine fibrosarcoma model

Lung colonization induced by the intravenous injection of fibrosarcoma cells into syngeneic mice was enhanced by the pretreatment of mice with cyclophosphamide (CPA), adriamycin (ADM), cis-diammine-dichloroplatinum II (DDP) and methotrexate (MTX). At equitoxic levels, CPA showed greater enhancement of the lung colonization than the other drugs treated. After a two-hour pretreatment of an endothelial monolayer culture, the adhesion of fibrosarcoma cells to endothelial cells was enhanced by all drugs, and the greatest enhancement was obtained with CPA. Data from these experiments supports the hypothesis that endothelial cell damag by anticancer drugs may facilitate metastasis of circulating tumor cells.