Src kinase contributes to the metastatic spread of carcinoma cells.
The involvement of Src kinase during carcinoma metastasis has been explored by using the NBT-II rat carcinoma cell line, which can be induced to scatter in vitro through Src activity. Here we show that Src activity was not required for growth of tumors derived from NBT-II cells injected into nude mice. In contrast, the presence of micrometastases was strictly dependent on Src, since the percentage of mice bearing metastases was dramatically reduced by the expression of a dominant-negative mutant of Src (SrcK-) or of Csk, the natural inhibitor of Src. Furthermore, metastatic cells originating from NBT-II cells displayed a Src activity higher than the parental cells, confirming that Src gives a selective advantage during the metastatic process. Finally, anatomopathological analysis of the primary tumors arising from NBT-II cells expressing Csk or SrcK- constructs revealed a highly differentiated epithelial phenotype contrasting with the poor differentiation of tumors derived from parental cells. The differentiated phenotype correlated with the presence of desmosomes at the cell periphery and the absence of vimentin intermediate filaments. Altogether, these data demonstrate that Src activity correlates with the loss of epithelial differentiation concomitantly with the increase of the metastatic potential of carcinoma cells.
Boyer
Brigitte
B
UMR 146 CNRS, Institut Curie, Section de Recherche, Bâtiment 110 Centre Universitaire Paris-Sud 91405 Orsay Cedex, France. Brigitte.Boyer@curie.u-psud.fr
Bourgeois
Yveline
Y
Poupon
Marie-France
MF
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009362:Neoplasm Metastasis; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D051381:Rats; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000473:pathology; D019061:src-Family Kinases / Q000235:genetics
D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D015688:Oncogene Protein pp60(v-src); D019061:src-Family Kinases