Research Papers:

Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH-Ras cancer cells: a PET imaging and metabolomics-mass-spectrometry study

Daniela Gaglio _, Silvia Valtorta, Marilena Ripamonti, Marcella Bonanomi, Chiara Damiani, Sergio Todde, Alfredo Simone Negri, Francesca Sanvito, Fabrizia Mastroianni, Antonella Di Campli, Gabriele Turacchio, Giuseppe Di Grigoli, Sara Belloli, Alberto Luini, Maria Carla Gilardi, Anna Maria Colangelo, Lilia Alberghina and Rosa Maria Moresco

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Oncotarget. 2016; 7:52017-52031. https://doi.org/10.18632/oncotarget.10470

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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

Correspondence to:

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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