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 e xpression of the components of the plasminogen, activation system duri ng progression to malignant melanoma with fresh melanocytic lesions. E xpression of these components is confined to late stages of melanoma. t-PA expression is limited to rare cases of metastatic melanoma. The o ther components are frequently expressed concomitantly in the same tum our. Urokinase (u-PA) is expressed in stromal cells and only in tumour cells at invasive foci, urokinase receptor (u-PAR) in tumour cells, p lasminogen activator inhibitor type I (PAI-1) in the intratumoral extr acellular matrix and plasminogen activator inhibitor type II (PAI-2) i n tumour cells and stromal cells. In order to investigate the role of u-PAR as a prognostic marker, we have developed an assay for quantitat ion of the receptor. As a first step towards stuctural investigations, we have determined the disulfide cross-links of the first domain of u PAR.