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VEGF targeted therapy stably modulates the glycolytic phenotype of tumor cells. (Articolo in rivista)

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VEGF targeted therapy stably modulates the glycolytic phenotype of tumor cells. (Articolo in rivista) (literal)

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Matteo Curtarello1, Elisabetta Zulato1, Giorgia Nardo2, Silvia Valtorta3, Giulia Guzzo4, Elisabetta Rossi5, Giovanni Esposito6, Aichi Msaki1, Anna Pasto7, Andrea Rasola4, Luca Persano8, Francesco Ciccarese2, Roberta Bertorelle1, Sergio Todde3, Mario Plebani9, Henrike Schroer10, Stefan Walenta11, Wolfgang Mueller-Klieser12, Alberto Amadori13, Rosa Maria Moresco14, and Stefano Indraccolo2 (2015)
VEGF targeted therapy stably modulates the glycolytic phenotype of tumor cells.
in Cancer research (Chic. Ill.)
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Matteo Curtarello1, Elisabetta Zulato1, Giorgia Nardo2, Silvia Valtorta3, Giulia Guzzo4, Elisabetta Rossi5, Giovanni Esposito6, Aichi Msaki1, Anna Pasto7, Andrea Rasola4, Luca Persano8, Francesco Ciccarese2, Roberta Bertorelle1, Sergio Todde3, Mario Plebani9, Henrike Schroer10, Stefan Walenta11, Wolfgang Mueller-Klieser12, Alberto Amadori13, Rosa Maria Moresco14, and Stefano Indraccolo2 (literal)

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1 Istituto Oncologico Veneto, Istituto Oncologico Veneto 2 UOC Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto 3 Nuclear Medicine Department, San Raffaele Scientific Institute 4 Department of Biomedical Sciences, University of Padova 5 Dept Oncology and Surgical Sciences, University of Padova 6 Istituto Oncologico Veneto (IOV), IRCCS, Istituto Oncologico Veneto (IOV), IRCCS 7 Istituto Oncologico Veneto IRCCS, Istituto Oncologico Veneto IRCCS 8 Dept. of Paediatrics, University of Padova 9 Dept. of Laboratory Medicine, Medical and Surgical Sciences, University of Padova 10 Institut für Physiologie und Pathophysiologie, Der Johannes Gutenberg-Universität Mainz 11 Physiology and Pathophysiology, Johannes Gutenberg Universitaet Mainz 12 Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz 13 Dept. of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy 14 nuclear medicine department and PET center, San Raffaele Scientific Institute, IBFM, CNR (literal)

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VEGF targeted therapy stably modulates the glycolytic phenotype of tumor cells. (literal)

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. (literal)

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