ENHANCED EXPRESSION OF UROKINASE PLASMINOGEN-ACTIVATOR AND ITS RECEPTOR IN PANCREATIC-CARCINOMA

Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in cancer invasion and metast asis. It binds to a specific membrane receptor denominated uPA recepto r (uPAR). uPA activates plasminogen to form plasmin, which participate s in tissue degradation and proteolysis. Binding of uPA to its recepto r accelerates UPA's own activation from pro-uPA, enhancing the activit y of the uPA/uPAR cascade. Using immunohistochemistry and Northern blo t analysis, we analysed the role of uPA and uPAR in 30 human pancreati c cancers. Immunohistochemical analysis demonstrated moderate to stron g immunostaining of both factors in most pancreatic cancers. Cancer le sions with signs of invasion exhibited the strongest immunohistochemic al signals for both factors. In addition, in desmoplastic areas adjace nt to the cancer cells, moderate uPA and uPAR immunoreactivity was det ectable. Northern blot analysis revealed a sixfold and a fourfold incr ease in uPA and uPAR mRNA levels in pancreatic cancer, respectively, i n comparison with normal controls (P<0.01). Correlation of the Norther n blot data with the clinical parameters of the patients indicated tha t patients with concomitant overexpression of uPA and uPAR had a short er post-operative survival (median 9 months; mean +/- s.d. 10.2 +/- 3. 6 months) than patients in whom only one or none of these factors were overexpressed (median 18 months; mean s.d. 20.3 +/- 8.7 months) (P<0. 002). Our data suggest that uPA and uPAR may serve as prognostic marke rs in human pancreatic cancer and that the marked overexpression of bo th factors may create an environment that enables pancreatic cancer ce lls to invade surrounding tissues.