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, S. Valtorta, M. Ripamonti, Marcella Bonanomi, Chiara Damiani, S. Todde, Alfredo Simone Negri, Francesca Sanvito, Fabrizia Mastroianni, Antonella Di Campli, Gabriele Turacchio, Giuseppe Di Grigoli, Sara Belloli, Alberto Luini, M. C. Gilardi, A. M. Colangelo, L. Alberghina, R. M. Moresco

Research output: Contribution to journalArticle

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 NIHRas 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.

Original languageEnglish
Pages (from-to)52017-52031
Number of pages15
JournalOncotarget
Volume7
Issue number32
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Metabolic rewiring
  • Metabolomics-mass-spectrometry
  • Oncogenic-K-ras
  • PET-imaging
  • Tumor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Gaglio, D., Valtorta, S., Ripamonti, M., Bonanomi, M., Damiani, C., Todde, S., Negri, A. S., Sanvito, F., Mastroianni, F., Campli, A. D., Turacchio, G., Di Grigoli, G., Belloli, S., Luini, A., Gilardi, M. C., Colangelo, A. M., Alberghina, L., & Moresco, R. M. (2016). Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH-Ras cancer cells: A PET imaging and metabolomics-mass-spectrometry study. Oncotarget, 7(32), 52017-52031. https://doi.org/10.18632/oncotarget.10470