title: Comparative metabolomics profiling of isogenic KRAS wild type and mutant NSCLC cells in vitro and in vivo.
abstract: Oncogenes induce metabolic reprogramming on cancer cells. Recently, G12C KRAS mutation in isogenic NSCLC cell line has been shown to be a key player in promoting metabolic rewiring mainly through the regulation of glutamine metabolism to fuel growth and proliferation. Even though cell lines possessing many of the genetic backgrounds of the primary cancer they derive from could be a valuable pre-clinical model, they do not have the additional complexity present in the whole tumor that impact metabolism. This preliminary study is aimed to explore how cancer cell metabolism in culture might recapitulate the metabolic alterations present in vivo. Our result highlighted that the gross metabolic changes observed in G12C KRAS mutant cells growing in culture were also maintained in the derived xenograft model, suggesting that a simple in vitro cell model can give important insights into the metabolic alterations induced by cancer. This is of relevance for guiding effective targeting of those metabolic traits that underlie tumor progression and anticancer treatment responses.
authors.affiliation: Protein and Gene Biomarkers Unit, Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brunelli
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caiola
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Protein and Gene Biomarkers Unit, Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D005973:Glutamine; D016283:Proto-Oncogene Proteins p21(ras)