TYPE-1 PLASMINOGEN ACTIVATOR INHIBITOR IN HUMAN RENAL CELL CARCINOMA

✍ Scribed by WAGNER, STEPHAN N.; ATKINSON, MICHAEL J.; THANNER, STEPHANIE; SCHMITT, MANFRED; WILHELM, OLAF; ROTTER, MICHAEL; HÖFLER, HEINZ

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 597 KB
• Volume: 179
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(199605)179:1<95::aid-path534>3.0.co;2-z

✦ Synopsis

In experimental models, plasminogen activator-mediated degradation of the extracellular matrix is inhibited by type-1 plasminogen activator inhibitor (PAI-1). PA14 has also been shown to protect tumour stromal tissue from autoproteolytic activities and may thus substantially promote tumour growth and metastasis formation. Human renal cell carcinoma (RCC) cells express significant amounts of plasminogen activator activity. In the present study, the expression of its specific inhibitor PAL1 has been investigated in 32 cases of RCC and compared with adjacent non-tumour renal tissues. RCC tissue exhibited higher levels of PAI-1, determined at both the antigen and the mRNA level by ELISA and Northern blot analysis respectively. Immunohistochemical analysis showed that PAL1 antigen was primarily confined to tumour cells and vascular 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 regulation of RCC-associated proteolysis. The increased expression of PAL1 and its predominant localization within the tumour may help to conserve tumour tissue integrity and may thus promote RCC progression and metastasis formation.