THE STATE OF DIFFERENTIATION OF HT-29 COLON-CARCINOMA CELLS ALTERS THE SECRETION OF CATHEPSIN-D AND OF PLASMINOGEN-ACTIVATOR

We have studied the cellular content and the extracellular release of cathepsins B and D, and of plasminogen activator, in 2 different tumor cell populations before confluence and after late confluence: the HT- 29 colon carcinoma cell line, which contains primarily undifferentiate d cells, and a subpopulation derived from this cell line, which contai ns primarily undifferentiated cells, which contains cells committed to differentiation into mucus-secreting goblet cells after confluence. I n both populations, cellular cathepsin-B activity increased after conf luence, and latent cathepsin B was found in all culture media. In the parental cell line, cellular cathepsin D activity decreased after conf luence; however, cathepsin D was secreted at high levels into the extr acellular medium. In contrast, in the subpopulation of cells committed to differentiation, cellular cathepsin D activity increased after con fluence, and cathepsin D was not secreted into the extracellular mediu m, but was immunolocalized in the apical brush border of the different iated cells. Plasminogen activator of urokinase type was identified by immunocytochemistry. Both subconfluent cell populations, and the post -confluent undifferentiated cell population, produced plasminogen acti vator activity at similar levels. In contrast, in the differentiated p ostconfluent cells, the production of plasminogen activator activity w as markedly lower. Our data show that the differentiation of HT-29 col on carcinoma cells into mucus-secreting cells impairs the secretion of plasminogen activator and cathepsin D, but does not affect cathepsin B. (C) 1994 Wiley-Liss, Inc.