Matrix metalloproteinases and plasminogen activation system components in pathogenesis and clinical course of colorectal cancer

Abstract

Herein we concisely review data on the role of tumor associated proteolytic systems in the realization of such important malignant tumor features as invasion and metastasizing. We also resume our own work on clinical value of plasminogen activation system components (uPA, tPA and PAI-1) and key matrix metalloproteases (MMP 2, 7, 9) and their tissue inhibitors (TIMP) in colorectal cancer. Two groups of patients were monitored for 5 or 10 years. The levels of the designated proteins were measured in plasma and/or tumor by immunoenzymatic techniques. High tumor PAI-1 (>4,0 ng/mg protein) concentration was shown to be significant and independent marker of poor prognosis of 5 and 10-year overall survival in stage III patients. High preoperative plasma levels of MMP-7 and TIMP-1 (cut-offs — 4,0 and 347 ng/ml, respectively) were shown to be independent unfavorable prognostic factors, and univariate analysis revealed unfavorable prognostic value of high tumor MMP-7 content (>7,8 ng/mg protein) in patients with disseminated process. Thus, it was shown that tumor associated proteases not only play an important role in the formation o f colorectal cancer invasive and metastatic potential, but also significantly affect clinical course of the disease.