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  • Original Paper
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Src kinase contributes to the metastatic spread of carcinoma cells

Oncogene volume 21, pages 2347–2356 (2002)Cite this article

Abstract

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.

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Acknowledgements

We thank Ana Maria Vallés for helpful discussion and for critical reading of the manuscript. We also thank Monique Denoyelle, Vincent Bordier and Christophe Alberti for their excellent technical assistance in animal experimentation. This project has been funded by the Centre National de la Recherche Scientifique (CNRS), the Association pour la Recherche contre le Cancer (ARC1321), the Ligue contre le Cancer, and Zeneca Pharma S.A. (AstraZeneca PLC).

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Authors and Affiliations

  1. UMR 146 CNRS, Institut Curie, Section de Recherche, Bâtiment 110 Centre Universitaire Paris-Sud, 91405, Orsay Cedex, France

    Brigitte Boyer & Yveline Bourgeois

  2. UMR 147 CNRS Institut Curie Section de Recherche, 26, rue d'Ulm, Paris, 75005, France

    Marie-France Poupon

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  1. Brigitte Boyer
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  2. Yveline Bourgeois
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Correspondence to Brigitte Boyer.

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Boyer, B., Bourgeois, Y. & Poupon, MF. Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene 21, 2347–2356 (2002). https://doi.org/10.1038/sj.onc.1205298

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