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  • Original Paper
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Gene expression profiling of normal human pulmonary fibroblasts following coculture with non-small-cell lung cancer cells reveals alterations related to matrix degradation, angiogenesis, cell growth and survival

Oncogene volume 22, pages 8487–8497 (2003)Cite this article

Abstract

Increasing evidence supports a major role for the microenvironment in carcinoma formation and progression. The influence of the stroma is partly mediated by signalling between epithelial tumor cells and neighboring fibroblasts. However, the molecular mechanisms underlying these interactions are largely unknown. To mimic the initial steps of invasive carcinoma in which tumor cells come in contact with normal stromal cells, we used a coculture model of non-small-cell lung cancer tumor cells and normal pulmonary fibroblasts. Using DNA filter arrays, we first analysed the overall modification of gene expression profile after a 24 h period of coculture. Next, we focused our interest on the transcriptome of the purified fibroblastic fraction of coculture using both DNA filter arrays and a laboratory-made DNA microarray. These experiments allowed the identification of a set of modulated genes coding for growth and survival factors, angiogenic factors, proteases and protease inhibitors, transmembrane receptors, kinases and transcription regulators that can potentially affect the regulation of matrix degradation, angiogenesis, invasion, cell growth and survival. This study represents to our knowledge the first attempt to dissect early global gene transcription occurring in a tumor–stroma coculture model and should help to understand better some of the molecular mechanisms involved in heterotypic signalling between epithelial tumor cells and fibroblasts.

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Acknowledgements

We thank Dr Walter Kisiel for providing TFPIs probes and specific antibodies. We also thank Dr Janine Gioanni and Christiane Mazeau for giving tumor-infiltrating fibroblasts from CAL33 tumor, Pr Margaret Shipp and Dr Jean Rosenbaum for helpful discussions and Dr Roser Busca for critical reading of the manuscript. We are grateful to Research Genetics technical support team for their help and Virginie Magnone for expert technical assistance.

This work has been supported by INSERM, Fondation de France, CNRS, University of Nice-Sophia Antipolis, the Ligue Nationale Contre le Cancer (Equipe labellisée), GIP Aventis 2/9936 and the Association pour la Recherche Contre le Cancer (ARC contrat 9502 and 9081). Olivia Fromigué is a recipient of a fellowship from the Fondation de France. We particularly thank the Fondation de France for their essential support (Programme Tumeurs Solides, contrat 99009531).

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Authors and Affiliations

  1. INSERM U526, IFR50, Faculté de Médecine Pasteur, Nice, France

    Olivia Fromigué, Krystel Louis, Patrick Auberger & Bernard Mari

  2. CNRS/UNSA UMR 6097, IPMC, Sophia Antipolis, France

    Manal Dayem & Pascal Barbry

  3. CNRS/UNSA UMR 6543, Centre Antoine Lacassagne, Nice, France

    Julie Milanini & Gilles Pages

  4. INSERM U385, IFR50, Faculté de Médecine Pasteur, Nice, France

    Sophie Tartare-Deckert & Gilles Ponzio

  5. INSERM EPI-0215, IFR50, Faculté de Médecine Pasteur, Nice, France

    Paul Hofman

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Fromigué, O., Louis, K., Dayem, M. et al. Gene expression profiling of normal human pulmonary fibroblasts following coculture with non-small-cell lung cancer cells reveals alterations related to matrix degradation, angiogenesis, cell growth and survival. Oncogene 22, 8487–8497 (2003). https://doi.org/10.1038/sj.onc.1206918

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