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Studies on functional and structural role of urokinase receptor and other components of the plasminogen activation system in malignancy.

Using immunohistochemistry and in-situ hybridization, we studied the expression of the components of the plasminogen activation system during progression to malignant melanoma with fresh melanocytic lesions. Expression of these components is confined to late stages of melanoma. t-PA expression is limited to rare cases of metastatic melanoma. The other components are frequently expressed concomitantly in the same tumour. Urokinase (u-PA) is expressed in stromal cells and only in tumour cells at invasive foci, urokinase receptor (u-PAR) in tumour cells, plasminogen activator inhibitor type I (PAI-1) in the intratumoral extracellular matrix and plasminogen activator inhibitor type II (PAI-2) in tumour cells and stromal cells. In order to investigate the role of u-PAR as a prognostic marker, we have developed an assay for quantitation of the receptor. As a first step towards structural investigations, we have determined the disulfide cross-links of the first domain of uPAR.