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 plasminoge n activators (PA), are elevated in many malignant tumors compared to t heir benign tumor counterparts, Extracellular matrix degradation media ted by PA may facilitate tumor cell invasion and metastasis, In this s tudy, the anti-proliferative activities of anti-urokinase-type plasmin ogen activator monoclonal antibodies (anti-UK MAbs) against human brea st cancer cell lines were tested. Immunofluorescence studies localized urokinase (UK) on the surfaces of breast cancer cells. Inhibition stu dies showed that anti-UK MAb concentrations exerted 50% inhibition of H-3-thymidine uptake by human breast cancer cell lines; CRL-1500 and C RL-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 cance r cells. Taken together, these results demonstrated the potential of a nti-UK MAbs to be a valuable reagent for cancer immunotherapy and anti -metastatic therapy.