Effects of 8-bromoadenosine 3':5'-cyclic monophosphate on proteolytic enzymes, adhesiveness and lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells.

Treatment of cloned low-metastatic Lewis lung carcinoma cells (P-29) with dimethylsulfoxide or butyric acid resulted in enhancement of their lung-colonizing ability. This was accompanied with increases in cathepsin B activity, the production of plasminogen activator, and adhesiveness, mainly heterotypic adhesion (adhesion to monolayers of endothelial cells) of dimethylsulfoxide-treated cells and homotypic aggregation of butyric acid-treated cells. Treatment of P-29 cells with 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP) also resulted in increases in cathepsin B activity and the production of plasminogen activator. However, it did not enhance either heterotypic adhesion or homotypic aggregation of the cells. The lung-colonizing ability of 8-bromo-cyclic AMP-treated P-29 cells was examined after their intravenous injection into male C57BL/6 mice. It was found that these cells did not have enhanced lung-colonizing ability. These results suggest that high activities of proteolytic enzymes such as cathepsin B and plasminogen activator in tumor cells are not sufficient alone for completing the metastatic process, but that other properties of tumor cells such as adhesiveness are also necessary.