TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR IN HUMAN RENAL-CELL CARCINOMA

In experimental models, plasminogen activator-mediated degradation of the extracellular matrix is inhibited by type-1 plasminogen activator inhibitor (PAI-1), PAI-1 has also been shown to protect tumour stromal tissue from autoproteolytic activities and may thus substantially pro mote tumour growth and metastasis formation, Human renal cell carcinom a (RCC) cells express significant amounts of plasminogen activator act ivity, In the present study, the expression of its specific inhibitor PAI-I has been investigated in 32 cases of RCC and compared with adjac ent non-tumour renal tissues, RCC tissue exhibited higher levels of PA I-I, determined at both the antigen and the mRNA level by ELISA and No rthern blot analysis respectively. Immunohistochemical analysis showed that PAI-I antigen was primarily confined to tumour cells and vascula r endothelium, a distribution similar to that previously reported for plasminogen activator activity in RCC, The close co-localization with endogenous plasminogen activator activity may be important in the regu lation of RCC-associated proteolysis. The increased expression of PAI- I and its predominant localization within the tumour mag help to conse rve tumour tissue integrity and may thus promote RCC progression and m etastasis formation.