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Rapid tumor development and potent vascularization are independent events in carcinoma producing FGF-1 or FGF-2

Oncogene volume 21, pages 8128–8139 (2002)Cite this article

Abstract

FGF-1 and FGF-2 are pleiotropic growth factors for many cell types, operating through the activation of specific transmembrane FGF receptors (FGFRs). The role of these factors in tumor progression was investigated, with specific discrimination between their autocrine and non autocrine cellular activity. The rat bladder carcinoma NBT-II cells were engineered to produce FGF-1 or 18 kDa FGF-2 in the presence or absence of their specific receptor. Non-autocrine cells that produced FGF-1 or FGF-2 but lacked FGFRs were epithelial and reminiscent of the parental NBT-II cells. Whilst autocrine cells, which both constitutively produced and secreted the growth factor and expressed FGFRs, had a highly invasive mesenchymal phenotype. Correspondingly, the autocrine cells were highly tumorigenic in vivo compared to the parental and non-autocrine cells, which correlated with the increased production of uPAR and active uPA and increased in vitro invasive potential. Although all cells produced VEGF, only tumors derived from cells that produced FGF-1 or FGF-2 were highly vascularized, suggesting that these two growth factors could be involved in the angiogenic process by activating host endothelial cells. As a result of activation of the FGFR in autocrine cells, changes in cell morphology and an increase in the invasive and tumorigenic properties were observed, however no in vitro or in vivo differential functions between FGF-1 and FGF-2 could be identified in this system. In conclusion, our data demonstrates that rapid tumor development is not dependent upon increased tumor vascularization, suggesting that ‘basal’ angiogenesis, probably mediated by VEGF, is sufficient to support tumor growth.

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Acknowledgements

We would like to thank Dr MF Poupon for nude mouse injections, Dr F Thierry for the FR3T3 cells, Dr MC Rio for the anti-rat MT1–MMP antibody, Dr M Jaye and Dr D Chopin for their anti-FGF-1 antibodies, Dr R Mudge and Dr M Morgan for useful discussions. This work was supported by the Centre National de la Recherche Scientifique and the Institut Curie, by grants from the Association pour la Recherche sur le Cancer (ARC-9477 and ARC-5902 to J Jouanneau), the Ligue Nationale Française contre le Cancer (National and Paris committees), the European Commission (B Janji) and the Groupement des Entreprises Françaises contre le Cancer (Gefluc).

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  1. Laboratory of Cell Morphogenesis and Tumor Progression, UMR 144 CNRS, Institut Curie, Section de recherche, 26 rue d'Ulm, Paris, cedex 05, 75248, France

    Clotilde Billottet, Bassam Janji, Jean-Paul Thiery & Jacqueline Jouanneau

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  1. Clotilde Billottet
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Correspondence to Jacqueline Jouanneau.

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Billottet, C., Janji, B., Thiery, JP. et al. Rapid tumor development and potent vascularization are independent events in carcinoma producing FGF-1 or FGF-2. Oncogene 21, 8128–8139 (2002). https://doi.org/10.1038/sj.onc.1205935

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