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The community effect in FGF-1 mediated tumor progression of a rat bladder carcinoma does not involve a direct paracrine signaling

Abstract

A community effect was found to occur between heterogeneous tumor cell populations leading to an overall increased tumorigenicity without a clonal dominance of the more tumorigenic clone. In the rat bladder carcinoma cell line NBT-II, this effect appears mediated by the Fibroblast Growth Factor-1 (FGF-1) through either a direct or an indirect signaling pathway. Neovascularization induced by FGF-1 was found not to be responsible for the community effect. The present study shows that the community effect does not involve a direct FGF-1 signaling since tumor cells expressing a dominant-negative FGF receptor mutant were still responding to the highly tumorigenic FGF-1 expressing cells. Tumors arising from inoculates of the FGF-1 producing NBT-II cells mixed with non tumorigenic epithelial MDCK cells contain only the tumorigenic cells indicating that MDCK cells may exerce a helper effect for the growth of the tumor not dependant on their own growth. Therefore the helper function of MDCK cells must be distinguished from a community effect where the contribution of low tumorigenic cells not only provides an in vivo growth advantage to few highly tumorigenic cells but become themselves highly tumorigenic indicating that the community effect may require cell-cell specific co-operativity independent from an helper effect.

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Acknowledgements

We want to thank R Warn for his kind gift of MDCK cells, M Jaye for the pFlg plasmid and recombinant FGF-1, T. Nakamura for the HGF/SF, H Prats for the recombinant FGF-2, A Garapin for the pAG60 plasmid, Y Bourgeois for the nude mouse injections and D Morineau for his help with the photographs. This work was supported by the Centre National de la Recherche Scientifique (CNRS) and the Institut Curie and by grants from the Association pour la Recherche sur le cancer (ARC- 4045), the Ligue Nationale française contre le Cancer and the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc).

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Jouanneau, J., Moens, G. & Thiery, J. The community effect in FGF-1 mediated tumor progression of a rat bladder carcinoma does not involve a direct paracrine signaling. Oncogene 18, 327–333 (1999). https://doi.org/10.1038/sj.onc.1202285

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