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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
Author(s) -
Abe Jinro,
Urano Tetsumei,
Konno Hiroyuki,
Erhan Yamaç,
Tanaka Tatsuo,
Nishino Nobuhiko,
Takada Akikazu,
Nakamura Satoshi
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19991215)86:12<2602::aid-cncr4>3.0.co;2-s
Subject(s) - urokinase receptor , plasminogen activator , colorectal cancer , cancer research , receptor , medicine , urokinase , plasminogen activator inhibitor 1 , lymph node , carcinoma , tumor progression , pathology , cancer
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) activity‐independent 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 ± 1.37 and 6.63 ± 7.49, respectively) in large tumors (≥50 mm in greatest dimension) than those in smaller tumors (< 50 mm) (2.50 ± 1.07 and 2.72 ± 2.70, respectively) ( P < 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI‐1/uPAR (r = 0.490; P < 0.0001) and PAI‐1/uPA (r = 0.469; P < 0.0001). In addition to liver metastases ( P = 0.004) and lymph node involvement ( P = 0.04), high levels of uPAR ( P = 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. Cancer 1999;86:2602–11. © 1999 American Cancer Society.