Platelets favor the outgrowth of established metastases

Maria J. Garcia-Leon (), Cristina Liboni, Vincent Mittelheisser, Louis Bochler, Gautier Follain, Clarisse Mouriaux, Ignacio Busnelli, Annabel Larnicol, Florent Colin, Marina Peralta, Naël Osmani, Valentin Gensbittel, Catherine Bourdon, Rafael Samaniego, Angélique Pichot, Nicodème Paul, Anne Molitor, Raphaël Carapito, Martine Jandrot-Perrus, Olivier Lefebvre, Pierre H. Mangin () and Jacky G. Goetz ()
Additional contact information
Maria J. Garcia-Leon: INSERM UMR_S1109
Cristina Liboni: INSERM UMR_S1109
Vincent Mittelheisser: INSERM UMR_S1109
Louis Bochler: INSERM UMR_S1109
Gautier Follain: INSERM UMR_S1109
Clarisse Mouriaux: Université de Strasbourg
Ignacio Busnelli: INSERM UMR_S1109
Annabel Larnicol: INSERM UMR_S1109
Florent Colin: INSERM UMR_S1109
Marina Peralta: INSERM UMR_S1109
Naël Osmani: INSERM UMR_S1109
Valentin Gensbittel: INSERM UMR_S1109
Catherine Bourdon: Université de Strasbourg
Rafael Samaniego: Unidad de Microscopía Confocal
Angélique Pichot: Université de Strasbourg
Nicodème Paul: Université de Strasbourg
Anne Molitor: Université de Strasbourg
Raphaël Carapito: Université de Strasbourg
Martine Jandrot-Perrus: Université Paris-Cité
Olivier Lefebvre: INSERM UMR_S1109
Pierre H. Mangin: Université de Strasbourg
Jacky G. Goetz: INSERM UMR_S1109

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47516-w

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