Collagen-mediated dispersion of NBT-II rat bladder carcinoma cells

During metastatic spread, locomotion mediated by extracellular matrix components of basement membranes and connective tissues has been invoked as a prerequisite to invasion. We studied the interactions of the rat bladder carcinoma cell line NBT-II with fibronectin, laminin, and collagens (types I, III, IV, and V). They all promoted cell attachment and spreading. To analyze their scatter potential, we studied epithelial outgrowth and/or peripheral cell dispersion from tumor aggregates. All matrix components allowed partial collapse of the aggregate and the appearance of a cellular monolayer forming a halo around the aggregate. No peripheral cell dispersion occurred on fibronectin and laminin. Collagens (especially types I and III) promoted the dispersion of peripheral NBT-II cells with various speeds of locomotion, as revealed by time-lapse videomicroscopy. With the exception of cells at the periphery on collagens, cells inside the halo did not exchange neighbors, migrated transiently as an epithelial sheet during halo formation, and finally remained stationary. These effects were reproduced with NBT-II tumor fragments obtained from nude mice. Tumor cells were linked together with desmosomes (as revealed by immunoreactivity against desmoglein). Migration on collagens correlated with the mechanical disruption of intercellular contacts and consequently with the progressive disappearance of desmoglein immunoreactivity. Immunofluorescence studies also revealed a reduced expression of the epithelium-specific cell adhesion molecule liver cell adhesion molecule after contact with collagens. These results suggest that direct interactions with collagens may favor single cell infiltration by bladder carcinoma.