6533b82efe1ef96bd12927ee
RESEARCH PRODUCT
VEGF-targeted therapy stably modulates the glycolytic phenotype of tumor cells
Giovanni EspositoRosa Maria MorescoElisabetta ZulatoHenrike SchroerFrancesco CiccareseMatteo CurtarelloAndrea RasolaWolfgang Mueller-klieserLuca PersanoStefan WalentaMario PlebaniAichi MsakiGiulia GuzzoStefano IndraccoloElisabetta RossiRoberta BertorelleAnna PastòAlberto AmadoriSilvia ValtortaSergio ToddeGiorgia Nardosubject
Vascular Endothelial Growth Factor ACancer ResearchPathologymedicine.medical_specialtyNecrosismedicine.medical_treatmentAngiogenesis InhibitorsMice SCIDBiologySCIDAntibodies Monoclonal HumanizedAntibodiesCell LineTargeted therapyMiceRandom AllocationCell Line TumorNeoplasmsMonoclonalAngiogenesis Inhibitors; Animals; Antibodies Monoclonal Humanized; Bevacizumab; Cell Line Tumor; Female; Glycolysis; Humans; MCF-7 Cells; Mice; Mice Inbred BALB C; Mice SCID; Molecular Targeted Therapy; Neoplasms; Phenotype; Random Allocation; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor AssaysmedicineAnimalsHumansGlycolysisMolecular Targeted Therapycancer-cellAnti-VEGF therapyHumanizedInbred BALB CMED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIAMice Inbred BALB CTumorpositron emission tomography antiangiogenesis glucose metabolism hypoxiaXenograft Model Antitumor AssaysPhenotypeBlockadeBevacizumabVascular endothelial growth factor APhenotypeOncologyCell cultureMonoclonalMCF-7 CellsCancer researchMED/06 - ONCOLOGIA MEDICAFemalemedicine.symptomGlycolysisdescription
Abstract Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this metabolic shift was stable and associated with increased tumor aggressiveness and resistance to VEGF blockade in serially transplanted mice. Our results support the hypothesis that the highly glycolytic phenotype of tumor cells studied in xenograft models, either primary or secondary, is a cell-autonomous trait conferring resistance to VEGF blockade. The finding that metabolic traits of tumors can be selected by antiangiogenic therapy suggests insights into the evolutionary dynamics of tumor metabolism. Cancer Res; 75(1); 120–33. ©2014 AACR.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-11-09 |