Comparative study of plasminogen activator antigens in colonic carcinomas and adenomas

Abstract

The correlation between malignant transformation and increased PA synthesis or secretion has been examined in a variety of cell lines. To study the relationship between content and composition of PAs and colorectal neoplasms, we measured u-PA and t-PA antigen levels in normal mucosa, tubular adenoma, adenocarcinoma in adenoma, and adenocarcinoma, using a sensitive sandwich enzyme immunoassay. This assay was very sensitive and was not hindered by the presence of serine protease inhibitors. Both adenomas and carcinomas had higher u-PA antigen levels than normal mucosa. The u-PA antigen level of adenomas was lower than that of carcinomas. Antigen level of t-PA, however, was lower in both adenomas and carcinomas compared with that in normal mucosa, the values being lowest in carcinomas. Two cases of carcinoma in adenoma had PA contents similar to those of carcinomas. u-PA antigen level of adenomas with dysplastic epithelium was higher than that of adenomas without dysplastic epithelium. Therefore, the increase of u-PA content in adenomas could be a parameter of malignant changes in adenomas.

Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas

“…In normal mucosa, the major source of plasminogen-mediated caseinolysis is due to tPA, hence the decreased level of plasminogen activation in adenomas can be assigned to lowered tPA activity. These histozymographic data on tPA are in agreement with the results of previous studies on tissue homogenates (de Bruin et al, 1988;Suzumiya et al, 1988;Sier et al, 1991a). Using antigen/activity immunosorbent methods together with an efficient tissue extraction procedure (Camiolo et al, 1982), we could demonstrate a clear-cut reduction in the tPA levels in adenomas compared with control and distant mucosae.…”

“…Moreover, the epithelial morphology may vary considerably among regions of individual adenomas. A microheterogeneity within adenomas might be a source of variations in previous works aiming at correlating the biochemical findings in adenoma tissue extracts with histological results in adjacent adenoma fragments (de Bruin et al, 1988;Sim et al, 1988;Suzumiya et al, 1988).In the present study, we have correlated the grade of epithelial cell dysplasia with the extent of plasminogen activation, as well as the tPA, uPA and PAI-I levels, in a series of large colorectal adenomas. To examine the relation between molecular changes and morphology, we have adapted the technique of histozymography to a semiquantitative assessment of plasmin generation in tissue sections.…”

“…A recent study reported that disturbances in the plasminogen activator system in the colorectum are maximal in invasive neoplasia (Delbaldo et al, 1995), but the data were only Received 10 March 1997 Revised 10 June 1997 Accepted 25 June 1997 Correspondence to: G Dorta qualitative and a relationship to the epithelial dysplasia in adenomas was not found. Studies examining a likely association between uPA levels and the grade of dysplasia in colorectal adenomas have reported contradictory results (de Bruin et al, 1988;Sim et al, 1988;Suzumiya et al, 1988;Sier et al, 1991b). Moreover, the epithelial morphology may vary considerably among regions of individual adenomas.…”

“…Previous studies have shown that tissue extracts from colorectal carcinomas have increased levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors (PAI) and decreased levels of tissue-type plasminogen activator (tPA) compared with morphologically normal adjacent mucosa (Gelister et al, 1986;Sier et al, 1991a). In adenomas, the levels of activators and inhibitors appear to be between those found in normal mucosa and those found in carcinoma (Gelister et al, 1986;Bruin et al, 1987;Sim et al, 1988;Suzumiya et al, 1988;Sier et al, 1991a). A recent study reported that disturbances in the plasminogen activator system in the colorectum are maximal in invasive neoplasia (Delbaldo et al, 1995), but the data were only Received 10 March 1997 Revised 10 June 1997 Accepted 25 June 1997 Correspondence to: G Dorta qualitative and a relationship to the epithelial dysplasia in adenomas was not found.…”

“…Moreover, the epithelial morphology may vary considerably among regions of individual adenomas. A microheterogeneity within adenomas might be a source of variations in previous works aiming at correlating the biochemical findings in adenoma tissue extracts with histological results in adjacent adenoma fragments (de Bruin et al, 1988;Sim et al, 1988;Suzumiya et al, 1988).…”