Metabolomics in cell culture—A strategy to study crucial metabolic pathways in cancer development and the response to treatment

Halama, Anna

doi:10.1016/j.abb.2014.09.002

Cited by 68 publications

(36 citation statements)

References 147 publications

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“…Extensive metabolic alterations occur when prostate cells experience neoplastic transformation. One of the most relevant alterations is citrate oxidation, because cancer cells are unable to accumulate zinc, and without elevated levels of zinc, m-aconitase is no longer inhibited and can catalyze citrate oxidation [2], [4], [27], [28], [30]. This transformation of citrate accumulation in healthy prostate cells to oxidized citrate in malignant prostate cells results in more efficient energy production.…”

Section: Altered Metabolism Of Pca Cellsmentioning

confidence: 99%

“…In addition, cell lines have a perfectly defined cell state which allows the analysis of a targeted metabolic status [2], [50], [51]. However, they do not efficiently simulate the complex cell-cell and cell-matrix interactions occurring within an organism [2], [52].…”

Section: Altered Metabolism Of Pca Cellsmentioning

confidence: 99%

“…Systems biology applied to cancer research encompasses the “omics” tools, including genomics, transcriptomics, proteomics, and metabolomics, which complement each other and are capable of measuring changes in several entities (genes, transcripts, proteins, or metabolites, respectively) simultaneously, providing an overview of various physiological or pathological conditions [1], [2], [3].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

Lima

Bastos

Carvalho

et al. 2016

Translational Oncology

117

113

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Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer death among men in Western countries. Current screening techniques are based on the measurement of serum prostate specific antigen (PSA) levels and digital rectal examination. A decisive diagnosis of PCa is based on prostate biopsies; however, this approach can lead to false-positive and false-negative results. Therefore, it is important to discover new biomarkers for the diagnosis of PCa, preferably noninvasive ones. Metabolomics is an approach that allows the analysis of the entire metabolic profile of a biological system. As neoplastic cells have a unique metabolic phenotype related to cancer development and progression, the identification of dysfunctional metabolic pathways using metabolomics can be used to discover cancer biomarkers and therapeutic targets. In this study, we review several metabolomics studies performed in prostatic fluid, blood plasma/serum, urine, tissues and immortalized cultured cell lines with the objective of discovering alterations in the metabolic phenotype of PCa and thus discovering new biomarkers for the diagnosis of PCa. Encouraging results using metabolomics have been reported for PCa, with sarcosine being one of the most promising biomarkers identified to date. However, the use of sarcosine as a PCa biomarker in the clinic remains a controversial issue within the scientific community. Beyond sarcosine, other metabolites are considered to be biomarkers for PCa, but they still need clinical validation. Despite the lack of metabolomics biomarkers reaching clinical practice, metabolomics proved to be a powerful tool in the discovery of new biomarkers for PCa detection.

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Section: Altered Metabolism Of Pca Cellsmentioning

confidence: 99%

Section: Altered Metabolism Of Pca Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

Lima

Bastos

Carvalho

et al. 2016

Translational Oncology

117

113

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“…It has been shown that abnormal vascularization of the tumor is promoting hypoxic conditions, which in turn can cause an increase in glucose uptake and lactate production8. The “Warburg effect” is one of the numerous of metabolic switches, identified in wide variaty of in vitro 9 and clinical studies10, which may potentially be regulated by the tumor microenvironment. Those interactions, although highly important from the perspective of identification of novel druggable targets and/or recognition of causal resistance mechanisms, are so far poorly defined.…”

mentioning

confidence: 99%

Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism

Halama

Guerrouahen

Pasquier

et al. 2017

Sci Rep

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The metabolic phenotype of a cancer cell is determined by its genetic makeup and microenvironment, which dynamically modulates the tumor landscape. The endothelial cells provide both a promoting and protective microenvironment – a niche for cancer cells. Although metabolic alterations associated with cancer and its progression have been fairly defined, there is a significant gap in our understanding of cancer metabolism in context of its microenvironment. We deployed an in vitro co-culture system based on direct contact of cancer cells with endothelial cells (E4+EC), mimicking the tumor microenvironment. Metabolism of colon (HTC15 and HTC116) and ovarian (OVCAR3 and SKOV3) cancer cell lines was profiled with non-targeted metabolic approaches at different time points in the first 48 hours after co-culture was established. We found significant, coherent and non-cell line specific changes in fatty acids, glycerophospholipids and carbohydrates over time, induced by endothelial cell contact. The metabolic patterns pinpoint alterations in hexosamine biosynthetic pathway, glycosylation and lipid metabolism as crucial for cancer – endothelial cells interaction. We demonstrated that “Warburg effect” is not modulated in the initial stage of nesting of cancer cell in the endothelial niche. Our study provides novel insight into cancer cell metabolism in the context of the endothelial microenvironment.

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“…Metabolic profiles of biofluids can be altered by a variety of physiological/pathological processes, and therefore global changes in such profiles may signal the presence of a particular disease state [7], [8], [9]. Oral or serum levels of metabolites in HNSCC cells have previously been profiled and compared with healthy volunteers [10], [11], [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma

Mukherjee

Funchain²,

Retuerto

et al. 2017

BBA Clinical

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BackgroundMetabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC.MethodsTumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS).ResultsAmong 28 samples obtained from 7 HNSCC cases and 7 controls, 422 metabolites were detected (269 identified and 153 unidentified). Oral washes contained 12 and 23 metabolites in healthy controls and HNSCC patients, respectively, with phosphate and lactate being the most abundant. Small molecules related to energy metabolism were significantly elevated in HNSCC patients compared to controls. Levels of beta-alanine, alpha-hydroxyisovalerate, tryptophan, and hexanoylcarnitine were elevated in HNSCC oral washes compared to healthy controls (range 7.8-12.2-fold). Resection tissues contained 22 metabolites, of which eight were overproduced in tumor by 1.9- to 12-fold compared to controls. TCA cycle analogs 2-hydroxyglutarate (2-HG) and 3-GMP were detected exclusively in tumor tissues. Targeted quantification of 2-HG in a representative HNSCC patient showed increase in tumor tissue (14.7 μg/mL), but undetectable in normal tissue. Moreover, high levels of 2-HG were detected in HNSCC cell lines but not in healthy primary oral keratinocyte cultures.ConclusionsOral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted.

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Metabolomics in cell culture—A strategy to study crucial metabolic pathways in cancer development and the response to treatment

Cited by 68 publications

References 147 publications

Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

Biomarker Discovery in Human Prostate Cancer: an Update in Metabolomics Studies

Nesting of colon and ovarian cancer cells in the endothelial niche is associated with alterations in glycan and lipid metabolism

Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma

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