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Platelets favor the outgrowth of established metastases

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  • Maria J. Garcia-Leon

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Cristina Liboni

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Vincent Mittelheisser

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Louis Bochler

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Gautier Follain

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Clarisse Mouriaux

    (Université de Strasbourg)

  • Ignacio Busnelli

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Annabel Larnicol

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Florent Colin

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Marina Peralta

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Naël Osmani

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Valentin Gensbittel

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Catherine Bourdon

    (Université de Strasbourg)

  • Rafael Samaniego

    (Unidad de Microscopía Confocal)

  • Angélique Pichot

    (Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG)

  • Nicodème Paul

    (Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG)

  • Anne Molitor

    (Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG)

  • Raphaël Carapito

    (Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg Transplantex NG
    1 Place de l’Hôpital)

  • Martine Jandrot-Perrus

    (Université Paris-Cité)

  • Olivier Lefebvre

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

  • Pierre H. Mangin

    (Université de Strasbourg)

  • Jacky G. Goetz

    (INSERM UMR_S1109
    Université de Strasbourg
    Fédération de Médecine Translationnelle de Strasbourg (FMTS)
    Equipe Labellisée Ligue Contre le Cancer)

Abstract

Despite abundant evidence demonstrating that platelets foster metastasis, anti-platelet agents have low therapeutic potential due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subject syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases via immune suppression. Genetic depletion and pharmacological targeting of the glycoprotein VI (GPVI) platelet-specific receptor in humanized mouse models efficiently reduce the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study demonstrates therapeutic efficacy when targeting animals bearing growing metastases. It further identifies GPVI as a molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.

Suggested Citation

  • Maria J. Garcia-Leon & Cristina Liboni & Vincent Mittelheisser & Louis Bochler & Gautier Follain & Clarisse Mouriaux & Ignacio Busnelli & Annabel Larnicol & Florent Colin & Marina Peralta & Naël Osman, 2024. "Platelets favor the outgrowth of established metastases," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47516-w
    DOI: 10.1038/s41467-024-47516-w
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    References listed on IDEAS

    as
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