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The role of cysteine and serine proteases in colorectal carcinoma
Author(s) -
Herszènyi Làszlò,
Plebani Mario,
Carraro Paolo,
De Paoli Massimo,
Roveroni Giovanni,
Cardin Romilda,
Tulassay Zsolt,
Naccarato Remo,
Farinati Fabio
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(19991001)86:7<1135::aid-cncr6>3.0.co;2-2
Subject(s) - proteases , cathepsin l , metastasis , cancer , plasminogen activator , colorectal cancer , cancer research , cathepsin b , cathepsin , medicine , biology , pathology , enzyme , biochemistry
BACKGROUND Cathepsin B (CATB) and cathepsin L (CATL), which are cysteine proteases, urokinase‐(UPA) and tissue‐type plasminogen activator (TPA), both serine proteases, and their inhibitor type‐1 (PAI‐1) are believed to play an important role in colorectal carcinoma (CRC) invasion and metastasis. The objective of this study was to measure CATB, CATL, UPA, TPA, and PAI‐1 in the same cancerous tissue (CANCER) and in tissues obtained from a tumor free area (NORMAL) to compare their respective prognostic roles in patients with CRC. METHODS CANCER and NORMAL samples were obtained from 60 CRC patients undergoing surgery (36 males and 24 females; mean age, 63.8 years [range, 27–85 years]). The antigen concentrations were measured using an enzyme‐linked immunoadsorbent assay method. The CANCER tissue also was examined in terms of major histomorphologic parameters such as differentiation, vascular invasion, degree of necrosis, and mucus production. RESULTS Significantly higher antigen levels were found: 1) in CANCER versus NORMAL (with respect to CATL, UPA, and PAI‐1, with significantly lower levels for TPA); 2) in CRC with versus without metastasis (CATB, CATL, and PAI‐1); 3) in poorly versus well differentiated CRC (UPA and PAI‐1); and 4) in advanced Dukes stages (PAI‐1). CATB and CATL significantly correlated with UPA and PAI‐1. Finally, CATL ( P = 0.0001), UPA ( P = 0.006), PAI‐1 ( P = 0.006), Dukes stage ( P = 0.0001), presence of metastases ( P = 0.003), and vascular invasion ( P = 0.03) had a significant prognostic impact. CONCLUSIONS The simultaneous up‐regulation of cysteine and serine proteases in CRC confirms their role in colorectal tumor biology and particularly in the process of invasion and metastasis. Together with Dukes stage, determinations of CATL, UPA, and PAI‐1 have a major prognostic impact in patients with CRC. Cancer 1999;86:1135–42. © 1999 American Cancer Society.