STUDIES OF POSSIBLE MECHANISMS FOR THE EFFECT OF UROKINASE THERAPY INSMALL-CELL CARCINOMA OF THE LUNG

Urokinase-type plasminogen activator has been administered by other in vestigators to patients with small cell carcinoma of the lung (SCCL) i n an attempt to induce lysis of fibrin that is known to exist in the c onnective tissue stroma of this tumour type and that may support tumou r growth. To study the fate of infused urokinase in this disease, a bi opsy of a scalp metastasis was obtained from a patient with SCCL (ente red on a phase I clinical trial of urokinase plus combination chemothe rapy) immediately following urokinase infusion during the fourth cours e of therapy at a time when this tumour mass had decreased to approxim ately 25% of its original size. Immunohistochemical procedures reveale d abundant stromal fibrin in accord with previous observations from th is laboratory. By contrast, urokinase, that is not a feature of small cell tumour cells, was present on the tumour cells in this specimen. U rokinase infusion was associated with a rapid increase in the amount o f this enzyme associated with isolated peripheral blood monocytes. The se results are consistent with uptake of infused urokinase onto monocy tes and possibly tumour cells. It is postulated that substantial tumou r fibrinolysis may not accompany such therapy and that urokinase, or i ts amino terminal fragment that bears the growth factor domain of this molecule, may bind to and alter the growth of the tumour cells.