Platelets favor the outgrowth of established metastases.
Fiche publication
Date publication
mai 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOETZ Jacky, Dr LEFEBVRE Olivier, Dr CARAPITO Raphaël, Dr MANGIN Pierre, Dr OSMANI Naël
Tous les auteurs :
Garcia-Leon MJ, Liboni C, Mittelheisser V, Bochler L, Follain G, Mouriaux C, Busnelli I, Larnicol A, Colin F, Peralta M, Osmani N, Gensbittel V, Bourdon C, Samaniego R, Pichot A, Paul N, Molitor A, Carapito R, Jandrot-Perrus M, Lefebvre O, Mangin PH, Goetz JG
Lien Pubmed
Résumé
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.
Mots clés
Animals, Blood Platelets, metabolism, Humans, Mice, Neoplasm Metastasis, Platelet Membrane Glycoproteins, metabolism, Cell Line, Tumor, Female, Mice, Inbred C57BL
Référence
Nat Commun. 2024 05 13;15(1):3297