Platelets favor the outgrowth of established metastases

: Garcia-Leon Maria J., Liboni Cristina, Mittelheisser Vincent, Bochler Louis, Follain Gautier, Mouriaux Clarisse, Busnelli Ignacio, Larnicol Annabel, Colin Florent, Peralta Marina, Osmani Naël, Gensbittel Valentin, Bourdon Catherine, Samaniego Rafael, Pichot Angélique, Paul Nicodème, Molitor Anne, Carapito Raphaël, Jandrot-Perrus Martine, Lefebvre Olivier, Mangin Pierre H., Goetz Jacky G.

Publisher: Springer Nature

: 2024

: Nature Communications

: Nature communications

: Nat Commun

: 3297

: 15

: 1

: 2041-1723

DOI: https://doi.org/10.1038/s41467-024-47516-w(external)

: https://www.nature.com/articles/s41467-024-47516-w(external)

: https://research.utu.fi/converis/portal/detail/Publication/404625025(external)

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.

s41467-024-47516-w.pdf