Résumé
The concept that immediate mobilization of bone marrow-derived circulating endothelial progenitor cells (CEPs) is a key mechanism mediating tumor resistance to vascular-disrupting agents (VDAs) has prevailed until now. Recently, we demonstrated that administration of a VDA to tumor-bearing mice induces two distinct peaks in CEPs: an early, unspecific CEP efflux after drug administration followed by a never-before-documented late yet more dramatic tumor-specific CEP burst which exclusively infiltrated tumors and incorporated neovessels in response to tumor hypoxia. Combined anti-angiogenic drugs could not disrupt the early peak but completely abrogated the late VDA-induced CEP burst, blunted bone marrow-derived cell recruitment to tumors, and resulted in striking antitumor efficacy, indicating that the late CEP burst was the actual source of tumor recovery after VDA therapy. In VDA-treated cancer patients, CEP kinetics were remarkably consistent with our preclinical data, evidencing a new mechanism that should be targeted to improve VDA-based strategies. These findings expand the current understanding of vasculogenic rebounds that may serve as biomarkers of resistance to VDA therapies that should be targeted to improve VDA-based strategies.
langue originale | Anglais |
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titre | Molecular Mechanisms of Angiogenesis |
Sous-titre | From Ontogenesis to Oncogenesis |
Editeur | Springer-Verlag France |
Pages | 445-460 |
Nombre de pages | 16 |
ISBN (Electronique) | 9782817804668 |
ISBN (imprimé) | 2817804651, 9782817804651 |
Les DOIs | |
état | Publié - 1 juil. 2014 |
Modification externe | Oui |