Progenitor endothelial cells as biomarkers of anti-vascular agents

Melissa Taylor, Françoise Farace

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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 originaleAnglais
titreMolecular Mechanisms of Angiogenesis
Sous-titreFrom Ontogenesis to Oncogenesis
EditeurSpringer-Verlag France
Pages445-460
Nombre de pages16
ISBN (Electronique)9782817804668
ISBN (imprimé)2817804651, 9782817804651
Les DOIs
étatPublié - 1 juil. 2014
Modification externeOui

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