Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH-Ras cancer cells: a PET imaging and metabolomics-mass-spectrometry study
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Daniela Gaglio1,2,6,8, Silvia Valtorta1,2,3,4, Marilena Ripamonti1,2, Marcella Bonanomi2, Chiara Damiani2, Sergio Todde5, Alfredo Simone Negri6, Francesca Sanvito7, Fabrizia Mastroianni2, Antonella Di Campli8, Gabriele Turacchio8, Giuseppe Di Grigoli1,2,3, Sara Belloli1,2,3, Alberto Luini8, Maria Carla Gilardi1,2, Anna Maria Colangelo2,9, Lilia Alberghina2,9,*, Rosa Maria Moresco2,3,4,*
1Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy
2SYSBIO.IT, Centre of Systems Biology, Milano, Italy
3Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
4Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
5Tecnomed Foundation of University of Milano-Bicocca, Monza, Italy
6Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy University of Milan, Milan, Italy
7Mouse Histopathology Unit, Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
8Institute of Protein Biochemistry, National Research Council, Naples, Italy
9Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy
*These authors have contributed equally to this work
Daniela Gaglio, email: [email protected]
Rosa Maria Moresco, email: [email protected]
Keywords: tumor, metabolic rewiring, PET-imaging, metabolomics-mass-spectrometry, oncogenic-K-ras
Received: February 02, 2016 Accepted: June 17, 2016 Published: July 07, 2016
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.
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