Anti-urokinase-type plasminogen activator monoclonal antibodies inhibit the proliferation of human breast cancer cell lines in vitro.

The levels of several tumor-associated proteases, including plasminogen activators (PA), are elevated in many malignant tumors compared to their benign tumor counterparts. Extracellular matrix degradation mediated by PA may facilitate tumor cell invasion and metastasis. In this study, the anti-proliferative activities of anti-urokinase-type plasminogen activator monoclonal antibodies (anti-UK MAbs) against human breast cancer cell lines were tested. Immunofluorescence studies localized urokinase (UK) on the surfaces of breast cancer cells. Inhibition studies showed that anti-UK MAb concentrations exerted 50% inhibition of 3H-thymidine uptake by human breast cancer cell lines; CRL-1500 and CRL-1504 were 5.6 x 10(-9)-1.82 x 10(-13) and 3.16 x 10(-10)-3.54 x 10(-12) M, respectively. Anti-UK MAbs exhibited little effect (10-20%) on normal human lymphocyte and liver cell lines. Dye exclusion indicated that anti-UK MAbs had a potent cytolytic effect on human breast cancer cells. Taken together, these results demonstrated the potential of anti-UK MAbs to be a valuable reagent for cancer immunotherapy and anti-metastatic therapy.