Changes in 2-fluoro-2-deoxy-d-glucose incorporation, hexokinase activity and lactate production by breast cancer cells responding to treatment with the anti-HER-2 antibody trastuzumab

Cheyne, Richard W.; Trembleau, Laurent; Mclaughlin, Abbie C.; Smith, T.

doi:10.1016/j.nucmedbio.2010.09.005

Cited by 17 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6B). This is consistent with several studies reporting reduced glucose uptake, decreased lactate secretion, and decreased glycolysis, in responsive HER2 overexpressing breast cancer cells treated with trastuzumab [35,36]. Treatment with both trastuzumab and tamoxifen decreased the redox ratio of responsive BT474 cells to levels seen in the non-cancerous MCF10A cell line (Fig.…”

Section: Discussionsupporting

confidence: 92%

Optical imaging of metabolism in HER2 overexpressing breast cancer cells

Walsh

Cook

Rexer

et al. 2011

Biomed. Opt. Express

View full text Add to dashboard Cite

The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.

show abstract

Section: Discussionsupporting

confidence: 92%

Optical imaging of metabolism in HER2 overexpressing breast cancer cells

Walsh

Cook

Rexer

et al. 2011

Biomed. Opt. Express

View full text Add to dashboard Cite

show abstract

“…However, this study illustrates the challenges of biological interpretation of metabolomics data. Relatively high levels of lactate and low levels of glucose are seen in HER2‐positive subjects, in line with the metabolic characteristics of HER2‐positive cell lines . The interpretation of this finding is that higher aerobic glycolysis in HER2‐positive tumors is reflected in the plasma metabolite levels.…”

Section: Disease Characterization and Prediction Of Prognosismentioning

confidence: 52%

NMR‐based metabolomics of biofluids in cancer

et al. 2018

View full text Add to dashboard Cite

This review describes the current status of NMR-based metabolomics of biofluids with respect to cancer risk assessment, detection, disease characterization, prognosis, and treatment monitoring. While the metabolism of cancer cells is altered compared with that of non-proliferating cells, the metabolome of blood and urine reflects the entire organism. We conclude that many studies show impressive associations between biofluid metabolomics and cancer progression, but translation to clinical practice is currently hindered by lack of validation, difficulties in biological interpretation, and non-standardized analytical procedures.

show abstract

“…While glucose withdrawal itself was sufficient to increase an starvation. [37][38][39][40] HER2 activates pathways that increase glucose transport into the cell along with a PI3K-dependent increase in AKT activity, a major signaling driving aerobic glycolysis. The mode of cell cycle arrest induced by glucose starvation in the absence or presence of metformin was examined by the propidium iodide DNA staining method and FACS analysis.…”

Section: Low-glucose Tumor Environmentmentioning

confidence: 99%