Increased expression of urokinase-type plasminogen activator in colorectal carcinoma and in adenomatous polyps

Human plasminogen activators (HPA) comprise the tissue type produced mainly by endothelial cells of 66 000 molecular weight (MW) which is principally involved in fibrinolysis (HPA66) and the urokinase type of 52 000 MW (HPA52) which is implicated in the invasion process of malignancy. The purpose of this study was to elucidate the pattern of HPA expression in histologically normal colonic mucosa, sporadic polyps, polyposis coli polyps, and in colon cancer tissue, to determine whether the expression of HPA52 is a correlate of neoplastic transformation of colonic epithelial cells. Homogenates of colonoscopic biopsies and resected colon tissue were subjected to polyacrylamide gel electrophoresis and the HPA activity was detected by a fibrin overlay gel. In histologically normal mucosal biopsies from non-cancer-bearing colons and in uninvolved mucosa from cancer-bearing colons, only HPA66 was detected. By contrast, all 19 colon cancer specimens expressed HPA52 and 16 of these also showed HPA66 activity. Two of three colon cancer cell lines showed HPA52 activity, but none expressed HPA66. HPA52 activity was observed in 17 of 20 adenomatous polyps, all of which displayed HPA66 activity. No correlation was found between polyp size, degree of epithelial dysplasia or the type of polyp architecture, and the semiquantitative estimates of HPA52 activity as judged by the areas of fibrinolysis generated.
This study of HPA52 in the colon epithelial neoplasms comprising adenomatous polyps, colon cancer tissue and colon cancer cell lines suggests that the transformation of the colon epithelial cell correlates with increased expression of HPA52, an enzyme that has been implicated in the invasive process of malignancy.