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Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition

Oncogene volume 27, pages 323–331 (2008)Cite this article

Abstract

Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phospho-isoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelial-mesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelial-mesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer.

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Author notes

  1. K M Sheehan and C Gulmann: These authors contributed equally to this study and are to be considered joint first authors.

Authors and Affiliations

  1. NCI-FDA Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    K M Sheehan, C Gulmann & L A Liotta

  2. Department of Pathology, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland

    K M Sheehan, C Gulmann, H L Barrett & E W Kay

  3. Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    G S Eichler & J N Weinstein

  4. Department of Epidemiology, Royal College of Surgeons in Ireland, Dublin, Ireland

    R M Conroy

  5. Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA

    L A Liotta & E F Petricoin III

  6. NCI-FDA Clinical Proteomics Program, Food and Drug Administration, Bethesda, MD, USA

    E F Petricoin III

Authors
  1. K M Sheehan
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  2. C Gulmann
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  3. G S Eichler
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  4. J N Weinstein
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  6. E W Kay
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  7. R M Conroy
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  8. L A Liotta
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  9. E F Petricoin III
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Correspondence to C Gulmann.

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Sheehan, K., Gulmann, C., Eichler, G. et al. Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition. Oncogene 27, 323–331 (2008). https://doi.org/10.1038/sj.onc.1210647

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  • DOI: https://doi.org/10.1038/sj.onc.1210647

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