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Model Systems of Carcinoma Cell Dispersion

  • Chapter
Attempts to Understand Metastasis Formation I

Part of the book series: Current Topics in Microbiology 213/I and Immunology ((CT MICROBIOLOGY,volume 213/1))

Abstract

The progressive loss of expression of a fully differentiated epithelial phenotype is a hallmark of carcinoma progression in both humans and animals. In the mouse skin system, for example, the loss of epithelial differentiation is accompanied by the appearance of malignant properties. In this well-studied system, chemical carcinogenesis generates multiple benign tumors, a proportion of which develop to form squamous cell carcinomas and, in extreme cases, spindle cell carcinomas that are highly invasive and metastatic tumors (Stoler et al. 1993). The transformation from squamous into spindle cells is characterized by the loss of epithelial features and the acquisition of a fibroblastic appearance. Analogous changes from an epithelial morphology to a fibroblast-like phenotype, correlating with the progression to malignancy, have also been observed in epithelial tumors derived from other sites, including colon and breast. Whether or not these phenotypic alterations can be regarded as authentic epithelium-to-mesenchyme transitions (EMTs), similar to those observed during embryogenesis, remains to be clarified. Nevertheless, since the maintenance of epithelial cell differentiation acts as a suppressor of malignancy (Harris 1990), it is essential to study the genetic and epigenetic events controlling the cellular program driving the transformation of epithelial cells into fibroblast-like cells. In that context, numerous in vitro models have been designed to clarify some aspects of tumor progression.Using this approach, several genes have been identified as potential tumor activators or suppressors: for example, E-cadherin, an epithelial cell adhesion molecule, has been demonstrated to act in vitro as a tumor suppressor gene (Frixen et al. 1991), while the mutant H-ras gene is rensponsible for the increased invasiveness of epithelial cell lines (Mareel et al. 1991).

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  1. Institut Curie, Section de Recherche, CNRS UMR 144, 26 rue d’Ulm, 75231, Paris Cedex 05, France

    B. Boyer, A. M. Vallés & J. P. Thiery

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  1. B. Boyer
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  2. A. M. Vallés
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  1. Basel Institute for Immunology, Grenzacherstraße 487, CH-4005, Basel, Switzerland

    Ursula Günthert Ph.D., P.D.

  2. Max-βDelbrūck-Centrum für Molekulare Medizin, Robert-Rōssle-Straße 10, D-13122, Berlin, Germany

    Walter Birchmeier Ph.D.

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Boyer, B., Vallés, A.M., Thiery, J.P. (1996). Model Systems of Carcinoma Cell Dispersion. In: Günthert, U., Birchmeier, W. (eds) Attempts to Understand Metastasis Formation I. Current Topics in Microbiology 213/I and Immunology, vol 213/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61107-0_11

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