The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study

Components of the plasmin system were comparatively studied in lymph node metastases and corresponding primary tumors by immunofluorescence. Primary tumors, all adenocarcinomas, originated from large bowel (N = 12) or breast (N = 10). We used antisera against plasminogen (Pg), plasminogen activators (PA) such as urokinase (UK) and tissue type PA (t-PA), plasmin inhibitors such as alpha 2 anti-plasmin (alpha 2AP) and alpha 2 macroglobulin (alpha 2M), plasmin-alpha 2 anti-plasmin complex (PAPC). Positivity with anti-PAPC serum was considered as proving that plasmin was formed by Pg activation. The following results were obtained. Breast adenocarcinomas were more strongly stained than colorectal adenocarcinomas using antisera against Pg, PAPC and PA, while their reactivity was much weaker with antisera against both plasmin inhibitors. Lymph node metastases from colorectal adenocarcinomas were more strongly stained than primary tumors using antisera against PAPC and PA. Reactivity with anti-Pg was similar, while that with antisera against plasmin inhibitors was much weaker. Metastasis from breast adenocarcinomas, on the average, showed the same type of staining as primary tumors. However, there was a slight decrease in reactivity with anti-Pg and PAPC in metastases. Tumor cells invading lymphoid areas in metastatic lymph nodes were often strongly labeled using antisera against Pg and UK. Staining was less strong or less frequent using antisera against PAPC and t-PA. These results favor the role of plasmin in the degradation of basement membrane and connective tissue components, thus implicating it in the invasiveness of tumor cells, at least in most primary tumors and metastases.