Direct in Vitro Lysis of Metastatic Tumor Cells by Cytokine-activated Murine Vascular Endothelial Cells

The purpose of these studies was to determine whether vascular endothelial cells can be treated with various cytokines to become cytotoxic against tumorigenic target cells under defined conditions in vitro. Microvascular endothelial cells were isolated from immunocompetent mice by perfusion of lungs grown in culture, cloned, and then characterized. The cloned microvascular endothelial cells were activated by incubation with a combination of recombinant tumor necrosis factor a and recombinant-γ interferon (10 units/ml each) for 24 h. Activated endothelial but not control endothelial cells (incubated in medium alone, recombinant tumor necrosis factor α alone, or recombinant γ interferon alone) produced significant lysis of mouse reticulum cell sarcoma and two different mouse melanomas. Moreover, at the concentrations used here, recombinant tumor necrosis factor α and recombinant γ interferon did not produce direct target cell lysis. The activated endothelial cell-mediated tumor cell lysis depended on the continuous presence of the cytokines and was not due solely to initial target cell binding. The results demonstrate that, like macrophages, microvessel endothelial cells exposed to low levels of cytokines are capable of lysing tumor cells.