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.

Abstract

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.

• Authors: J Abe, T Urano, H Konno, Y Erhan, T Tanaka, N Nishino, A Takada, S Nakamura
• Journal: Cancer (Cancer) Vol. 86 Issue 12 Pg. 2602-11 (Dec 15 1999) ISSN: 0008-543X [Print] United States
• PMID: 10594855 (Publication Type: Journal Article)
• Copyright: Copyright 1999 American Cancer Society.

Chemical References

• PLAUR protein, human
• Plasminogen Activator Inhibitor 1
• Plasminogen Activator Inhibitor 2
• Receptors, Cell Surface
• Receptors, Urokinase Plasminogen Activator
• Urokinase-Type Plasminogen Activator

Topics

• Adult
• Aged
• Carcinoma (metabolism, pathology, secondary)
• Colorectal Neoplasms (blood, metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Humans
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Staging
• Plasminogen Activator Inhibitor 1 (blood, metabolism)
• Plasminogen Activator Inhibitor 2 (blood, metabolism)
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Receptors, Cell Surface (blood, metabolism)
• Receptors, Urokinase Plasminogen Activator
• Survival Analysis
• Urokinase-Type Plasminogen Activator (blood, metabolism)