ENHANCED METASTATIC POTENTIAL OF CLONED LOW-METASTATIC LEWIS LUNG-CARCINOMA CELLS TREATED INVITRO WITH DIMETHYLSULFOXIDE

Abstract

Treatment of low-metastatic Lewis lung carcinoma cells (P-29) with dimethyl sulfoxide [DMSO] in vitro enhanced their lung-colonizing ability. The concentration of DMSO used delayed the in vitro growth of P-29 cells but was not cytotoxic. The arrest and retention in the lung of untreated and DMSO treated P-29 cells labeled with 5-[125I]iodo-2''-deoxyuridine after injecting them into a tail vein of syngeneic mice were examined. DMSO-treated P-29 cells were trapped in the lung more than untreated cells and were cleared from the lungs more slowly than untreated cells. Treatment of P-29 cells with DMSO resulted in the increase in their homotypic aggregation and adhesion to plastic culture dishes, monolayers of endothelial cells, and a subendothelial extracellular matrix. This treatment also increased significantly their activities of degradative enzymes, such as glycosidases and cathepsin B, and their production of plasminogen activator. The enhanced lung-colonizing ability of P-29 cells treated with DMSO is due to the increase in adhesiveness, resulting in arrest and retention of the cells in the lung of the host and in the increase in their degradative enzyme activities. The enhancing effect of DMSO on the lung-colonizing ability of P-29 cells was reversible.