Metabolic signatures of malignant progression in prostate epithelial cells

Teahan, Orla; Bevan, Charlotte L.; Waxman, Jonathan; Keun, Hector C.

doi:10.1016/j.biocel.2010.07.003

Cited by 46 publications

(32 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although many prostate biobanks storing fresh tissue have been established, this paper is the first to present results from an integrative design bringing together transcript and metabolite profiles. The benefit of using human tissue is the possibility to overcome the limitations of using immortalized cell models with "normal" physiologic phenotypes (30). However, the histopathologic evaluation was carried out on cryosections of each sample and was somewhat impaired by freezing artifacts, which were prominent in some samples.…”

Section: Limitation and Strength Of The Studymentioning

confidence: 99%

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Bertilsson

Tessem

Flatberg

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Low concentrations of citrate and high concentrations of choline-containing compounds (ChoCC) are metabolic characteristics observed by magnetic resonance spectroscopy of prostate cancer tissue. The objective was to investigate the gene expression changes underlying these metabolic aberrations to find regulatory genes with potential for targeted therapies.Experimental design: Fresh frozen samples (n ¼ 133) from 41 patients undergoing radical prostatectomy were included. Histopathologic evaluation was carried out for each sample before a metabolic profile was obtained with high-resolution magic angle spinning (HR-MAS) spectroscopy. Following the HR-MAS, RNA was extracted from the same sample and quality controlled before carrying out microarray gene expression profiling. A partial least square statistical model was used to integrate the data sets to identify genes whose expression show significant covariance with citrate and ChoCC levels.Results: Samples were classified as benign, n ¼ 35; cancer of low grade (Gleason score 6), n ¼ 24; intermediate grade (Gleason score 7), n ¼ 41; or high grade (Gleason score !8), n ¼ 33. RNA quality was high with a mean RNA Integrity Number score of 9.1 (SD 1.2). Gene products predicting significantly a reduced citrate level were acetyl citrate lyase (ACLY, P ¼ 0.003) and m-aconitase (ACON, P < 0.001). The two genes whose expression most closely accompanied the increase in ChoCC were those of phospholipase A2 group VII (PLA2G7, P < 0.001) and choline kinase a (CHKA, P ¼ 0.002).Conclusions: By integrating histologic, transcriptomic, and metabolic data, our study has contributed to an expanded understanding of the mechanisms underlying aberrant citrate and ChoCC levels in prostate cancer.

show abstract

Section: Limitation and Strength Of The Studymentioning

confidence: 99%

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Bertilsson

Tessem

Flatberg

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…The high frequency of this disease has resulted in the establishment of a national screening program to improve early diagnosis, which is crucial for patient outcome. The high specificity and low invasiveness are critical prerequisites for any potent biomarker; therefore, improvement in the recently applied screening of prostate specific antigen (PSA) and/or the development of additional biomarkers is required [121]. Lately, the implementation of metabolomics towards the identification of metabolic signatures of patients with prostate cancer (who express low levels of PSA) reveals a linkage between a decreased citrate level and cancer progression [122].…”

Section: Metabolomics and Prostate Cancer Cell Linesmentioning

confidence: 99%

“…However, metabolic pathways associated with malignant transformation, have not been detected by studying human biofluids until now. To address this issue, metabolomics has been applied in the normal epithelial prostate cell line (RWPE-1) and in cancer cell lines with low invasiveness (WPE1-NB14) and high invasiveness (WPE1-NB11) [121], that are model systems for investigating prostate cancer progression and malignancy [123]. An approach based on the implementation of high-resolution 1H-NMR spectroscopy resulted in the assignment of unique metabolic profiles for each cell line.…”

Section: Metabolomics and Prostate Cancer Cell Linesmentioning

confidence: 99%

“…In addition, extracellular lactate and alanine perturbation corresponded to the stage of malignancy. Thus, a pool of molecules is presented, which content should be further validated as biomarkers for the aggressiveness of prostate cancer in the biofluids [121]. Because androgen and androgen receptor are the known players in prostate cancer progression and malignancy development, metabolomics at the cellular level was implemented to uncover biochemical processes regulated by androgen signalling [124].…”

Section: Metabolomics and Prostate Cancer Cell Linesmentioning

confidence: 99%

See 1 more Smart Citation

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

Halama¹

2014

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

“…36 Employing NMR spectroscopic analysis of cell media and aqueous extracts of cell pellets allowed measurement of the intracellular and extracellular metabolic profiles in the different cell lines. The malignant cell line showed aberrant intracellular levels of various metabolites including choline and branched-chain amino acids.…”

Section: Oncologymentioning

confidence: 99%

CHAPTER 3. High‐Resolution NMR‐Based Metabolic Profiling in Drug Discovery and Development

Waters¹

2013

New Applications of NMR in Drug Discovery and Development

View full text Add to dashboard Cite

The application of NMR spectroscopy in the field of biology and medicine has grown consistently and steadily over the last 40 years or so, with the advancements in high field magnets, computational infrastructure and probe technology all aiding its progress to what is now a fundamental tool in the life sciences. Moreover, it has played an ever-increasing role in a plethora of applications within drug discovery and development including compound structure elucidation and chemical characterization, macromolecule secondary and tertiary structure determination, measurement of molecular dynamics and rates of turnover and magnetic resonance imaging (MRI). One area where NMR spectroscopy has really proved invaluable is that of metabolic profiling. The first reported application of NMR to metabolic profiling was in 1974, when Hoult et al. measured the complement of phosphorus-containing metabolites in isolated skeletal muscle by 31 P NMR spectroscopy. 1 This early work culminated in the emergence of a whole new field of metabolism science, which has in recent years been termed metabonomics or metabolomics, to describe the

show abstract

Metabolic signatures of malignant progression in prostate epithelial cells

Cited by 46 publications

References 61 publications

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

Changes in Gene Transcription Underlying the Aberrant Citrate and Choline Metabolism in Human Prostate Cancer Samples

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

CHAPTER 3. High‐Resolution NMR‐Based Metabolic Profiling in Drug Discovery and Development

Contact Info

Product

Resources

About