Dataset Information

Stable Isotope-Resolved Metabolomic Differences between Hormone-Responsive and Triple-Negative Breast Cancer Cell Lines.

ABSTRACT:

Purpose

To conduct an exploratory study to identify mechanisms that differentiate Luminal A (BT474 and MCF-7) and triple-negative (MDA-MB-231 and MDA-MB-468) breast cancer (BCa) cell lines to potentially provide novel therapeutic targets based on differences in energy utilization.

Methods

Cells were cultured in media containing either [U-¹³C]-glucose or [U-¹³C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by ¹H and ¹³C NMR spectroscopy.

Results

MCF-7 cells consumed the most glucose, producing the most lactate, demonstrating the greatest Warburg effect-associated energy utilization. BT474 cells had the highest tricarboxylic acid cycle (TCA) activity. The majority of energy utilization patterns in MCF-7 cells were more similar to MDA-MB-468 cells, while the patterns for BT474 cells were more similar to MDA-MB-231 cells. Compared to the Luminal A cell lines, TNBC cell lines consumed more glutamine and less glucose. BT474 and MDA-MB-468 cells produced high amounts of ¹³C-glycine from media [U-¹³C]-glucose which was integrated into glutathione, indicating de novo synthesis.

Conclusions

Stable isotopic resolved metabolomics using ¹³C substrates provided mechanistic information about energy utilization that was difficult to interpret using ¹H data alone. Overall, cell lines that have different hormone receptor status have different energy utilization requirements, even if they are classified by the same clinical BCa subtype; and these differences offer clues about optimizing treatment strategies.

SUBMITTER: Winnike JH

PROVIDER: S-EPMC6186330 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Stable Isotope-Resolved Metabolomic Differences between Hormone-Responsive and Triple-Negative Breast Cancer Cell Lines.

Winnike Jason H JH Stewart Delisha A DA Pathmasiri Wimal W WW McRitchie Susan L SL Sumner Susan J SJ

International journal of breast cancer 20180930

<h4>Purpose</h4>To conduct an exploratory study to identify mechanisms that differentiate Luminal A (BT474 and MCF-7) and triple-negative (MDA-MB-231 and MDA-MB-468) breast cancer (BCa) cell lines to potentially provide novel therapeutic targets based on differences in energy utilization.<h4>Methods</h4>Cells were cultured in media containing either [U-<sup>13</sup>C]-glucose or [U-<sup>13</sup>C]-glutamine for 48 hours. Conditioned media and cellular extracts were analyzed by <sup>1</sup>H and ...[more]

PMID: 30363973

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Dataset Information

Stable Isotope-Resolved Metabolomic Differences between Hormone-Responsive and Triple-Negative Breast Cancer Cell Lines.

Purpose

Methods

Results

Conclusions

Publications

Stable Isotope-Resolved Metabolomic Differences between Hormone-Responsive and Triple-Negative Breast Cancer Cell Lines.

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