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.
Document Type
Article
Publication Date
9-2017
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.ymben.2017.01.010
Funding Information
This work was funded by the Komen Foundation [BCTR0503648], NIH [5R21CA133668-02, 1U24DK097215-01A1], and the Kentucky Challenge for Excellence.
Related Content
Refer to Web version on PubMed Central for supplementary material.
Repository Citation
Lane, Andrew N.; Tan, Julie; Wang, Yali; Yan, Jun; Higashi, Richard M.; and Fan, Teresa W. -M., "Probing the Metabolic Phenotype of Breast Cancer Cells by Multiple Tracer Stable Isotope Resolved Metabolomics" (2017). Center for Environmental and Systems Biochemistry Faculty Publications. 6.
https://uknowledge.uky.edu/cesb_facpub/6
Supplementary Materials
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Cell and Developmental Biology Commons, Oncology Commons
Notes/Citation Information
Published in Metabolic Engineering, v. 43, part B, p. 125-136.
© 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
The document available for download is the author's post-peer-review final draft of the article.