Correlations between cell surface protease activities and abnormalities of occludens junctions in rat bladder carcinoma in vitro.

Microenvironmental alterations, i.e., proteolytic enzymes, may play a causative role in abnormalities of zonulae occludentes. To test this hypothesis, we compared in vitro the ultrastructure of three carcinoma cell lines which were derived from N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced tumors of the rat urinary bladder. One of these lines had a high cell surface protease activity; the other two lines exhibited relatively low activities. Quantitative electron microscopy data revealed differences in configuration and distribution of zonula occludens-intramembrane fibrils among these cell lines, as indicated by means and standard deviations of zonulae occludens widths, and numbers of intramembrane fibrils. Although the total length of the intramembranous fibrils per square micrometer of occludens junction area was not statistically different in the three lines, junctional morphology varied greatly. Thus, carcinoma cells with high surface protease activities are able to synthesize near-normal amounts of intramembrane fibrils but are unable to assemble normal zonulae occludentes. This indicates that alterations in zonula occludens morphology, which have been induced by exogenous proteolytic enzymes, are identical to those observed in a cell line with high cell surface protease activity.