Combined effects of extracellular matrix and growth factors on NBT-II rat bladder carcinoma cell dispersion.
Using the rat bladder carcinoma cell line NBT-II we showed that collagens but not laminin and fibronectin were able to induce cell scattering. Acidic fibroblast growth factor and transforming growth factor alpha also promoted NBT-II cell dispersion on glass or tissue culture plastic. We have now further analysed the scatter response to these two growth factors in the presence of extracellular matrix molecules. In the presence of growth factors, no peripheral single-cell dispersion occurred on fibronectin and laminin, although time-lapse video analyses revealed intense cell mingling and motility inside the monolayer forming around NBT-II aggregates. Patterns of strings or files of cells protruding from the monolayer were often observed. The presence of a scattering activity in the complex acellular extracellular matrix deposited by NBT-II cells themselves strongly suggested that substratum conditioning was responsible for this effect. On the other hand, the two growth factors accelerated collagen-mediated NBT-II individual cell dispersion and locomotion in a reversible way. As a marker of cell dissociation, we studied desmosome distribution in aggregate cultures: desmosomes were present in aggregates formed in suspension even in the presence of growth factors, whereas internalization occurred after cell-to-substratum contact. On laminin or fibronectin and in the presence of growth factors, peripheral cells inside the halo of NBT-II aggregates did not exhibit desmosome linkages. These observations suggest that scatter effects per se are dependent on the composition of the extracellular matrix. In particular, on a substratum nonpermissive for direct cell translocation, individual cell dispersion can be replaced by en bloc patterns of migration following substratum conditioning by the cells.
Tucker
G C
GC
Laboratoire de Physiopathologie du Développement, CNRS URA 1337 Ecole Normale Supérieure, Paris, France.
Boyer
B
B
Valles
A M
AM
Thiery
J P
JP
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000032:analysis; D051180:Desmoplakins; D003896:Desmosomes / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D005353:Fibronectins; D007797:Laminin; D016211:Transforming Growth Factor alpha; D016220:Fibroblast Growth Factor 1