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. Cancer 1999;86:2602–11. © 1999 American Cancer Society.

Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer

“…Tumour cells simultaneously secrete proteases (uPA) and their inhibitors (PAI-1), and the balance between the two precisely regulates the level of extracellular proteolysis, thus either promoting or suppressing angiogenesis (Folkman et al, 2001). It is likely that excess PAI-1 decreases cell adhesion to the extracellular matrix by interfering with uPAR binding to vitronectin, thus facilitating cell invasion and migration (Abe et al, 1999). Other reports have also indicated that excess PAI-1 plays an important role in tumour growth and metastasis by stimulating angiogenesis (McMahon et al, 2001;Bajou, 2002;Devy et al, 2002).…”

Analysis of expressions of components in the plasminogen activator system in high- and low-metastatic human lung cancer cells

“…In these processes, PAI-1 can bind to uPAR-bound uPA and results in internalization of the PAI-1:uPA:uPAR complex, leading to degradation of PAI-1 and uPA and recycle of uPAR on the cell surface (Nykjaer et al 1997). Many clinical and experimental studies have proved that the high expression of uPA, uPAR, and PAI-1 was closely related to the unfavorable prognosis of tumors (Harbeck et al 1999;Abe et al 1999;Knoop et al 1998). uPA, uPAR, and PAI-1 levels were considered as independent and signi®cant prognostic markers.…”

Urokinase Receptor and Vascular Endothelial Growth Factor Are Synergistically Associated with the Liver Metastasis of Colorectal Cancer

“…----------------been shown to be the most substantial determinant of the overall survival rate in patients with colorectal cancer, 36) we focused on the role of the PA system and VEGF in the liver metastasis of colorectal cancer.…”