TY - JOUR
T1 - Platelets favor the outgrowth of established metastases
AU - Garcia-Leon, Maria J.
AU - Liboni, Cristina
AU - Mittelheisser, Vincent
AU - Bochler, Louis
AU - Follain, Gautier
AU - Mouriaux, Clarisse
AU - Busnelli, Ignacio
AU - Larnicol, Annabel
AU - Colin, Florent
AU - Peralta, Marina
AU - Osmani, Naël
AU - Gensbittel, Valentin
AU - Bourdon, Catherine
AU - Samaniego, Rafael
AU - Pichot, Angélique
AU - Paul, Nicodème
AU - Molitor, Anne
AU - Carapito, Raphaël
AU - Jandrot-Perrus, Martine
AU - Lefebvre, Olivier
AU - Mangin, Pierre H.
AU - Goetz, Jacky G.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
UR - https://www.mendeley.com/catalogue/5e7f7ef6-c28e-3b60-81ec-1b7e82fe16ca/
U2 - 10.1038/s41467-024-47516-w
DO - 10.1038/s41467-024-47516-w
M3 - Article
C2 - 38740748
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3297
ER -