Serine proteinase activation in esophageal cancer.
BACKGROUND
Activation of the plasminogen/plasmin system seems to contribute to tumor aggressiveness and shorter post-operative survival. In the present study we examined the relation of uPA (urokinase plasminogen activator), uPAR (uPA receptor) and PAI-1 (plasminogen activator inhibitor type 1) to the biological growth behavior of esophageal cancer, as well as their influence on survival in esophageal cancer.


METHODS
The expression and distribution of uPA, uPAR and PAI-1 were analyzed by Northern blot analysis and immunostaining in 41 resected esophageal cancers and in normal esophagi.


RESULTS
Northern blot analysis revealed a 5.0-, 3.6- and 5.4-fold increase in uPA, uPAR, and PAI-1 mRNA levels in esophageal cancer, respectively, in comparison to normal controls (p<0.01). These mRNA moieties were concomitantly increased in 86% of the tumors. uPA activity was 2.3-fold increased in esophageal cancer compared with normal controls (p<0.01). Statistical analysis revealed no differences in uPA, uPAR and PAI-1 immunoreactivity between well-differentiated, moderately-differentiated and poorly-differentiated tumors. Furthermore, survival analysis showed no difference in patients whose tumors exhibited positive uPA and uPAR immunostaining (median 11 months, range 4-36 months) versus patients whose tumors exhibited negative uPA and uPAR immunostaining (median 11 months, range 3-51 months).


CONCLUSIONS
Our data revealed that overexpression of uPA, uPAR and PAI-1 is often present in human esophageal carcinomas. However, up-regulation of these factors is not correlated with tumor differentiation or survival. These findings indicate that, unlike other tumors, uPA, uPAR and PAI-1 seem not to be prognostic markers for esophageal carcinomas.
Tang
W H
WH
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Friess
H
H
Kekis
P B
PB
Martignoni
M E
ME
Fukuda
A
A
Roggo
A
A
Zimmerman
A
A
Büchler
M W
MW
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism*
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator