Platelets favor the outgrowth of established metastases

• Published in: Nature communications Vol. 15; no. 1; pp. 3297 - 19
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/51; 14; 14/19; 14/5; 45/91; 631/67/1059; 631/67/322; 64/116; 64/60; Animal models; Animals; Binding; Blood Platelets - drug effects; Blood Platelets - metabolism; Cell Line, Tumor; Female; Glycoprotein VI; Glycoproteins; Hematology; Hemorrhage; Human health and pathology; Humanities and Social Sciences; Humans; Life Sciences; Metastases; Metastasis; Mice; Mice, Inbred C57BL; multidisciplinary; Neoplasm Metastasis; Pharmacology; Platelet Membrane Glycoproteins - genetics; Platelet Membrane Glycoproteins - metabolism; Platelets; Receptors; Science; Science (multidisciplinary); Tumor cells; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47516-w

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. It is unclear if platelets regulate the growth of established metastases. Using syngeneic mouse models of metastasis, the authors show that platelets support the outgrowth of established metastases via immune suppression, and that targeting the platelet-specific receptor GPVI, efficiently reduces established metastases, providing a promising therapeutic avenue for inhibiting cancer metastasis.