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

作者：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

来源：Oncotarget, 2016, 7(32): 52017-52031.

DOI：10.18632/oncotarget.10470

• tumor
• metabolic rewiring
• PET-imaging
• metabolomics-mass-spectrometry
• oncogenic-K-ras

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.

• 出版日期2016-8-9