Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics

Andrew N. Lane, Julie Tan, Yali Wang, Jun Yan, Richard M. Higashi, Teresa W.M. Fan

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using 13C6-glucose, 13C-1+2-glucose, 13C5,15N2-Gln, 13C3-glycerol, and 13C8-octanoate as tracers. These tracers were designed to probe the central energy producing and anabolic pathways (glycolysis, pentose phosphate pathway, Krebs Cycle, glutaminolysis, nucleotide synthesis and lipid turnover). We found that glycolysis was not associated with the rate of breast cancer cell proliferation, glutaminolysis did not support lipid synthesis in primary breast or breast cancer cells, but was a major contributor to pyrimidine ring synthesis in all cell types; anaplerotic pyruvate carboxylation was activated in breast cancer versus primary cells. We also found that glucose metabolism in individual breast cancer cell lines differed between in vitro cultures and tumor xenografts, but not the metabolic distinctions between cell lines, which may reflect the influence of tumor architecture/microenvironment.

Original languageEnglish
Pages (from-to)125-136
Number of pages12
JournalMetabolic Engineering
Volume43
DOIs
StatePublished - Sep 2017

Bibliographical note

Publisher Copyright:
© 2017 International Metabolic Engineering Society

Keywords

  • 1D/2D NMR
  • Breast cancer metabolism
  • C
  • C-glucose
  • C-glycerol
  • C-octanoate
  • FT-ICR-MS
  • Mouse xenografts
  • N-Gln
  • Stable isotope-resolved metabolomics

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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