CXCL10 reduces melanoma proliferation and invasiveness in vitro and in vivo

Authors

  • F. Antonicelli,

    1. Laboratoire de Dermatologie, Université de Reims Champagne-Ardenne, CNRS UMR-6237, IFR53, UFR Médecine, Reims, France
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  • J. Lorin,

    1. Service de Dermatologie, Université de Reims Champagne-Ardenne, CHU de Reims, Hôpital Robert Debré, Reims, France
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  • S. Kurdykowski,

    1. Laboratoire de Dermatologie, Université de Reims Champagne-Ardenne, CNRS UMR-6237, IFR53, UFR Médecine, Reims, France
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  • S.C. Gangloff,

    1. Laboratoire d’Immunologie et de Microbiologie, Université de Reims Champagne-Ardenne, EA 4303, IFR53, UFR de Pharmacie, Reims, France
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  • R. Le Naour,

    1. Laboratoire d’Immunologie et de Microbiologie, Université de Reims Champagne-Ardenne, EA 4303, IFR53, UFR de Pharmacie, Reims, France
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  • J.M. Sallenave,

    1. Institut Pasteur, Unité de Défense Innée et Inflammation (§) INSERM U874, (†) Université Paris, Paris, 7-Diderot (#), France
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  • W. Hornebeck,

    1. Laboratoire de Dermatologie, Université de Reims Champagne-Ardenne, CNRS UMR-6237, IFR53, UFR Médecine, Reims, France
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  • F. Grange,

    1. Laboratoire de Dermatologie, Université de Reims Champagne-Ardenne, CNRS UMR-6237, IFR53, UFR Médecine, Reims, France
    2. Service de Dermatologie, Université de Reims Champagne-Ardenne, CHU de Reims, Hôpital Robert Debré, Reims, France
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  • P. Bernard

    1. Laboratoire de Dermatologie, Université de Reims Champagne-Ardenne, CNRS UMR-6237, IFR53, UFR Médecine, Reims, France
    2. Service de Dermatologie, Université de Reims Champagne-Ardenne, CHU de Reims, Hôpital Robert Debré, Reims, France
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  • Funding sources
    This work has been supported by grants from CNRS, Ligue contre le Cancer (Comité de la Marne), SRD (Société de Recherche Dermatologique), SFD (Société Française de Dermatologie) and University Hospital of Reims.

  • Conflicts of interest
    None declared.

Philippe Bernard.
E-mail: pbernard@chu-reims.fr

Summary

Background  Melanoma is often infiltrated by inflammatory and immune cells that might either maintain chronic inflammation, therefore promoting tumour growth, or mount an antitumour response to control tumour outcome. In this setting, Th1-oriented lymphocyte infiltration is associated with a better outcome in melanoma. Although the interferon-induced protein CXCL10 is expressed by Th1 immune cells, its receptor was also shown to be involved in melanoma progression and metastasis.

Objectives  To investigate the CXCL10-mediated antitumoral response in vivo, and its clinical relevance.

Methods  C57BL/6 mice bearing B16F1 melanoma were treated intraperitoneally with an adenovirus vector expressing CXCL10. In addition, peripheral blood mononuclear cells (PBMC) from 20 patients, 10 with melanoma in remission and 10 with melanoma in progression, were assessed for their cytokine/chemokine content using a 30-plex assay, and for their ability to modulate melanoma invasion in vitro in Transwell® (Sigma-Aldrich) chambers coated with Matrigel® (BD Biosciences).

Results  Treatment with CXCL10 reduced melanoma tumour growth in C57BL/6 mice compared with controls in vivo, and reduced melanoma invasion in vitro. Screening for expression of 30 cytokine/chemokine proteins showed that only CXCL10 was significantly increased in patients in remission compared with patients in progression. PBMC only from patients in remission significantly reduced melanoma cell invasiveness in an ex vivo Transwell® assay. Accordingly, this inhibitory effect was also observed with PBMC culture media from patients with melanoma in remission.

Conclusions  The quantitative increase in CXCL10 production, together with its ability to limit melanoma progression, shows the potential benefit of this chemokine to control melanoma progression or metastasis.

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