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

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...

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Published in:Oncotarget 2016-08, Vol.7 (32), p.52017-52031
Main Authors: Gaglio, Daniela, Valtorta, Silvia, Ripamonti, Marilena, Bonanomi, Marcella, Damiani, Chiara, Todde, Sergio, Negri, Alfredo Simone, Sanvito, Francesca, Mastroianni, Fabrizia, Di Campli, Antonella, Turacchio, Gabriele, Di Grigoli, Giuseppe, Belloli, Sara, Luini, Alberto, Gilardi, Maria Carla, Colangelo, Anna Maria, Alberghina, Lilia, Moresco, Rosa Maria
Format: Article
Language:English
Subjects:
Animals
Genes, ras - genetics
Glycolysis
Mass Spectrometry
Metabolomics - methods
Mice
Mice, Nude
Neoplasms, Experimental - diagnostic imaging
Neoplasms, Experimental - genetics
Neoplasms, Experimental - metabolism
NIH 3T3 Cells
Positron-Emission Tomography - methods
Research Paper
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.10470