Plasminogen activators, activation inhibitors and alpha2-macroglobulin produced by cultured normal and malignant human cells

Abstract

In the present paper we have characterized the plasminogen activators (PA) synthesized by 25 different human cell lines. Technically easy methods were adopted for concentration and immunological characterization of the activators even in the presence of PA inhibitors. Most cell lines produced u‐PA (mol. wt 55,000), melanoma and HeLa cells t‐PA (mol. wt 66,000) and two carcinoma cell lines and normal skin fibroblasts produced no detectable PA. The classical ¹²⁵I‐fibrin method was compared to a caseinolytic assay and some of the discrepancies between results obtained with the two methods were shown to be due to cell‐derived NaDodSO₄‐sensitive proteinase inhibitors in culture media. Additionally, synthesis and uptake by the cells of the wide‐spectrum proteinase inhibitor alpha‐2‐macroglobulin (alpha₂M) were studied by radioimmunoassay and immunofluorescence. No production of alpha₂M could be measured in any of the malignant cell lines. In normal cells no correlation existed between the production of alpha₂M and the observed inhibition of PA activity, which indicates that other proteinase inhibitors are produced by the cells.