Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model

Authors

  • F. Rambow,

    Corresponding author
    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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    • Both authors contributed equally to this work.

  • O. Malek,

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
    2. Institute of Animal Physiology and Genetics, 27721 Libechov, Czech Republic
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    • Both authors contributed equally to this work.

  • C. Geffrotin,

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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  • J.-J. Leplat,

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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  • S. Bouet,

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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  • G. Piton,

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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  • K. Hugot,

    1. INRA, DGA, Centre de Ressources Biologiques Gadie, Jouy-en-Josas, F-78352 France
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  • C. Bevilacqua,

    1. INRA, DGA, Plateau d’instrumentation et de compétences en transcriptomique, Jouy-en-Josas, F-78352 France
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  • V. Horak,

    1. Institute of Animal Physiology and Genetics, 27721 Libechov, Czech Republic
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  • S. Vincent-Naulleau

    1. CEA, DSV, IRCM, SREIT, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France; INRA, DGA, Laboratoire de Radiobiologie et d’Etude du Génome, Jouy-en-Josas, F-78352 France
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Address correspondence to F. Rambow, e-mail: florian.rambow@jouy.inra.fr

Summary

Partial and some few cases of complete spontaneous regression have been observed in cutaneous melanoma patients but little is known about the molecular mechanisms involved. The Melanoblastoma-bearing Libechov Minipig (MeLiM) is a suitable animal model to study the phenomenon of spontaneous regression because MeLiM pigs exhibit naturally occurring melanomas which regress completely 6 months after birth. In this study, we used suppression subtractive hybridization (SSH) to identify molecular determinants of melanoma regression within swine melanoma tissues and melanoma cell cultures. Several markers involved in cell-adhesion, -communication, -motility, signal transduction, negative regulation of cell proliferation, transport and immune response were identified that correlated with melanoma regression whereas the main genes involved in melanin synthesis showed a strong downregulation. For the most differentially expressed genes, we validated the results obtained by SSH with qRT-PCR and with immunohistochemistry for some of them (CD9, MITF, RARRES1). Most notable, for the first time in melanoma, we identified the retinoic acid responder 1 gene (RARRES1) as a main actor of the regression process in melanoma. This first gene expression study in swine melanoma regression, may contribute to the finding of new therapeutic targets for human melanoma treatment.

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