title: Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH-Ras cancer cells: a PET imaging and metabolomics-mass-spectrometry study.
abstract: Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cells and tumors are able to coordinate nutrient utilization to support aggressive cell proliferation and survival. Using PET imaging and metabolomics-mass spectrometry, we identified the activation of multiple metabolic pathways such as: glycolysis, autophagy recycling mechanism, glutamine and serine/glycine metabolism, both under physiological and under stress conditions. Finally, differential responses between in vitro and in vivo systems emphasize the advantageous and uncontrolled nature of the in vivo environment, which has a pivotal role in controlling the responses to therapy.
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy University of Milan, Milan, Italy.|Institute of Protein Biochemistry, National Research Council, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gaglio
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Valtorta
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Ripamonti
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Bonanomi
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Damiani
authors.affiliation: Tecnomed Foundation of University of Milano-Bicocca, Monza, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Todde
authors.affiliation: Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy University of Milan, Milan, Italy.
authors.forename: Alfredo Simone
authors.initials: AS
authors.lastname: Negri
authors.affiliation: Mouse Histopathology Unit, Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanvito
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Mastroianni
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Campli
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Turacchio
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Grigoli
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Belloli
authors.affiliation: Institute of Protein Biochemistry, National Research Council, Naples, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.affiliation: Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy.|SYSBIO.IT, Centre of Systems Biology, Milano, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Gilardi
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Colangelo
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.affiliation: SYSBIO.IT, Centre of Systems Biology, Milano, Italy.|Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
mesh_terms: D000818:Animals; D011905:Genes, ras / Q000235:genetics; D006019:Glycolysis; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods
keywords: PET-imaging; metabolic rewiring; metabolomics-mass-spectrometry; oncogenic-K-ras; tumor