Studies of possible mechanisms for the effect of urokinase therapy in small cell carcinoma of the lung.

Urokinase-type plasminogen activator has been administered by other investigators to patients with small cell carcinoma of the lung (SCCL) in an attempt to induce lysis of fibrin that is known to exist in the connective tissue stroma of this tumour type and that may support tumour growth. To study the fate of infused urokinase in this disease, a biopsy of a scalp metastasis was obtained from a patient with SCCL (entered on a phase I clinical trial of urokinase plus combination chemotherapy) immediately following urokinase infusion during the fourth course of therapy a time when this tumour mass had decreased to approximately 25% of its original size. Immunohistochemical procedures revealed abundant stromal fibrin in accord with previous observations from this laboratory. By contrast, urokinase, that is not a feature of small cell tumour cells, was present on the tumour cells in this specimen. Urokinase infusion was associated with a rapid increase in the amount of this enzyme associated with isolated peripheral blood monocytes. These results are consistent with uptake of infused urokinase onto monocytes and possibly tumour cells. It is postulated that substantial tumour fibrinolysis may not accompany such therapy and that urokinase, or its amino terminal fragment that bears the growth factor domain of this molecule, may bind to and alter the growth of the tumour cells.