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Metastasis signatures: genes regulating tumor–microenvironment interactions predict metastatic behavior

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Abstract

The possibility of predicting clinical outcome of cancer patients through the analysis of gene expression profiles in the primary tumor is a kind of ideological revolution as the multistep carcinogenesis model postulates that the proportion of cells within the primary tumor that actually acquire metastasis driving mutation(s) is small; too small to leave its imprint on the gene expression profile. The data collected to date have brought a new paradigm to reality in the metastasis field: metastasis must at least in part rely on mutations and/or gene regulation events present in the majority of cells which constitute the primary tumor mass. By analyses of differential expression of primary tumors versus metastases or by functional analyses of putative metastasis genes in experimental metastasis, many metastasis-associated gene expression events have been identified that correlate with the development of metastases. Among genes “favoring” metastasis, we find many molecules that are expressed not by the tumor cell itself but by the cells of the microenvironment, as well as genes over-expressed in the primary tumor that have a principle role in mediating tumor–host interactions. Here we review these concepts and advance hypotheses on how gene expression of the primary tumor and the microenvironment can favor the spread of the metastasis seeds and how this knowledge can provide tools to secondary prevention.

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Acknowledgements

We thank Ambra Zuccarino for their help with the data analysis and Douglas Noonan (University of Insubria, Varese) for critical reading. We thank Paola Corradino (Advanced Biotechnology Center, Genova) and Virginia Dolcini (IRCCS MultiMedica, Milan) for data management and revision of the manuscript. The authors acknowledge contributions from following institutions: AIRC, Ministero della Salute, Istituto Superiore della Sanità, Ministero dell’Istruzione, dell’Università e della Ricerca, Progetto Fondo per gli investimenti della ricerca di base (FIRB-LITBIO), Progetto Comitato Interministeriale per la Programmazione Economica-Regione Liguria, Compagnia San Paolo di Torino, Fondazione CARIGE.

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  1. IRCCS MultiMedica, Scientific and Technological Pole, Via Fantoli 16/15, 20138, Milan, Italy

    Adriana Albini

  2. Functional Genomics, National Cancer Research Institute, Genoa, Italy

    Valentina Mirisola & Ulrich Pfeffer

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  1. Adriana Albini
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Albini, A., Mirisola, V. & Pfeffer, U. Metastasis signatures: genes regulating tumor–microenvironment interactions predict metastatic behavior. Cancer Metastasis Rev 27, 75–83 (2008). https://doi.org/10.1007/s10555-007-9111-x

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