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Larger and more invasive colorectal carcinoma contains larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlates well with tumor size

✍ Scribed by Jinro Abe; Tetsumei Urano; Hiroyuki Konno; Yamaç Erhan; Tatsuo Tanaka; Nobuhiko Nishino; Akikazu Takada; Satoshi Nakamura


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
130 KB
Volume
86
Category
Article
ISSN
0008-543X

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✦ Synopsis


BACKGROUND.

Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase-type plasminogen activator (uPA) activityindependent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated.

METHODS.

In 100 colorectal carcinoma patients, antigen levels of u-PA, uPAR, and PAI-1 and PAI-2 were assayed in both tumor tissues and their normal counterparts.

Plasma levels of soluble uPAR also were determined.

RESULTS.

All uPAR, uPA, PAI-1, and PAI-2 antigen levels in tumor tissue were significantly higher than those in normal tissue. Levels of both uPAR and PAI-1 were significantly higher (3.09 Ϯ 1.37 and 6.63 Ϯ 7.49, respectively) in large tumors (Ն50 mm in greatest dimension) than those in smaller tumors (Ͻ 50 mm) (2.50 Ϯ 1.07 and 2.72 Ϯ 2.70, respectively) (P Ͻ 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI-1/uPAR (r ϭ 0.490; P Ͻ 0.0001) and PAI-1/uPA (r ϭ 0.469; P Ͻ 0.0001). In addition to liver metastases (P ϭ 0.004) and lymph node involvement (P ϭ 0.04), high levels of uPAR (P ϭ 0.05) also were found to be of independent prognostic value by multivariate analysis.

CONCLUSIONS. Higher expression of uPAR was related to poor prognosis of patients

with colorectal carcinoma and excess amounts of PAI-1 over uPAR or uPAR-bound uPA appeared to play an important role in tumor progression.