Limits...
Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells.

Burch TC, Isaac G, Booher CL, Rhim JS, Rainville P, Langridge J, Baker A, Nyalwidhe JO - PLoS ONE (2015)

Bottom Line: We have identified potentially interesting species of different lipid subclasses including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), glycerophosphoinositols (PIs) and other metabolites that are significantly upregulated in prostate cancer cells derived from distant metastatic sites.Transcriptomic and biochemical analysis of key enzymes that are involved in lipid metabolism demonstrate the significant upregulation of choline kinase alpha in the metastatic cells compared to the non-malignant and non-metastatic cells.This suggests that different de novo lipogenesis and other specific signal transduction pathways are activated in aggressive metastatic cells as compared to normal and non-metastatic cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States of America; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia, United States of America.

ABSTRACT
Prostate cancer (PCa) is the most prevalent cancer amongst men and the second most common cause of cancer related-deaths in the USA. Prostate cancer is a heterogeneous disease ranging from indolent asymptomatic cases to very aggressive life threatening forms. The goal of this study was to identify differentially expressed metabolites and lipids in prostate cells with different tumorigenic phenotypes. We have used mass spectrometry metabolomic profiling, lipidomic profiling, bioinformatic and statistical methods to identify, quantify and characterize differentially regulated molecules in five prostate derived cell lines. We have identified potentially interesting species of different lipid subclasses including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), glycerophosphoinositols (PIs) and other metabolites that are significantly upregulated in prostate cancer cells derived from distant metastatic sites. Transcriptomic and biochemical analysis of key enzymes that are involved in lipid metabolism demonstrate the significant upregulation of choline kinase alpha in the metastatic cells compared to the non-malignant and non-metastatic cells. This suggests that different de novo lipogenesis and other specific signal transduction pathways are activated in aggressive metastatic cells as compared to normal and non-metastatic cells.

No MeSH data available.


Related in: MedlinePlus

Tandem mass spectrometry spectrum.Fragmentation trace for compound 8.13_759.5775n in the positive ion mode with the identification of PC (16:0/18:1(9Z)) (1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526693&req=5

pone.0134206.g002: Tandem mass spectrometry spectrum.Fragmentation trace for compound 8.13_759.5775n in the positive ion mode with the identification of PC (16:0/18:1(9Z)) (1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm.

Mentions: The identification of the metabolites was based on exact mass precursor ion, theoretical isotopic distribution, retention time and high energy fragment ion information. To improve the confidence in the compound identification theoretical, fragmentation of a candidate list of compounds was performed and then matched to the resulting ‘in silico’ fragmentation against the measured fragments for a compound. The candidate molecules were selected from compound databases (LipidMAPS database for lipids and Human Metabolome Database (HMDB) for polar metabolites) based on the exact mass within a specified error range given in parts per million (ppm). Using this list of candidates, the fragmentation algorithm generates all possible fragments for a candidate compound in order to match the fragment mass with the measured peaks in the experimental data. The measured spectra are then matched against the in silico fragment ions. The different lipid species of PC, PE, PS, PI and TG are listed with the two fatty acyl groups separated with a slash, e.g. PC 16:0/18:1. Fig 2 shows a representative fragmentation trace for compound 8.13_759.5775n in the positive mode lipidomics experiments with the identification of PC(16:0/18:1) (1-hexadecanoyl-2-(octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm. In this approach, lipid species are identified at level of head group plus total acyl carbons: total double bonds. The detected intensities, each defined by an intact ion mass/charge (m/z) and a characteristic fragment m/z, are herein described as ‘‘apparent lipid molecular species”.


Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells.

Burch TC, Isaac G, Booher CL, Rhim JS, Rainville P, Langridge J, Baker A, Nyalwidhe JO - PLoS ONE (2015)

Tandem mass spectrometry spectrum.Fragmentation trace for compound 8.13_759.5775n in the positive ion mode with the identification of PC (16:0/18:1(9Z)) (1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526693&req=5

pone.0134206.g002: Tandem mass spectrometry spectrum.Fragmentation trace for compound 8.13_759.5775n in the positive ion mode with the identification of PC (16:0/18:1(9Z)) (1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm.
Mentions: The identification of the metabolites was based on exact mass precursor ion, theoretical isotopic distribution, retention time and high energy fragment ion information. To improve the confidence in the compound identification theoretical, fragmentation of a candidate list of compounds was performed and then matched to the resulting ‘in silico’ fragmentation against the measured fragments for a compound. The candidate molecules were selected from compound databases (LipidMAPS database for lipids and Human Metabolome Database (HMDB) for polar metabolites) based on the exact mass within a specified error range given in parts per million (ppm). Using this list of candidates, the fragmentation algorithm generates all possible fragments for a candidate compound in order to match the fragment mass with the measured peaks in the experimental data. The measured spectra are then matched against the in silico fragment ions. The different lipid species of PC, PE, PS, PI and TG are listed with the two fatty acyl groups separated with a slash, e.g. PC 16:0/18:1. Fig 2 shows a representative fragmentation trace for compound 8.13_759.5775n in the positive mode lipidomics experiments with the identification of PC(16:0/18:1) (1-hexadecanoyl-2-(octadecenoyl)-sn-glycero-3-phosphocholine). The measured spectra which are matched against the in silico fragment ions are highlighted in red. The circle on the top of the red spectra shows the structure, measured m/z, theoretical m/z and corresponding mass error in ppm. In this approach, lipid species are identified at level of head group plus total acyl carbons: total double bonds. The detected intensities, each defined by an intact ion mass/charge (m/z) and a characteristic fragment m/z, are herein described as ‘‘apparent lipid molecular species”.

Bottom Line: We have identified potentially interesting species of different lipid subclasses including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), glycerophosphoinositols (PIs) and other metabolites that are significantly upregulated in prostate cancer cells derived from distant metastatic sites.Transcriptomic and biochemical analysis of key enzymes that are involved in lipid metabolism demonstrate the significant upregulation of choline kinase alpha in the metastatic cells compared to the non-malignant and non-metastatic cells.This suggests that different de novo lipogenesis and other specific signal transduction pathways are activated in aggressive metastatic cells as compared to normal and non-metastatic cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States of America; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia, United States of America.

ABSTRACT
Prostate cancer (PCa) is the most prevalent cancer amongst men and the second most common cause of cancer related-deaths in the USA. Prostate cancer is a heterogeneous disease ranging from indolent asymptomatic cases to very aggressive life threatening forms. The goal of this study was to identify differentially expressed metabolites and lipids in prostate cells with different tumorigenic phenotypes. We have used mass spectrometry metabolomic profiling, lipidomic profiling, bioinformatic and statistical methods to identify, quantify and characterize differentially regulated molecules in five prostate derived cell lines. We have identified potentially interesting species of different lipid subclasses including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), glycerophosphoinositols (PIs) and other metabolites that are significantly upregulated in prostate cancer cells derived from distant metastatic sites. Transcriptomic and biochemical analysis of key enzymes that are involved in lipid metabolism demonstrate the significant upregulation of choline kinase alpha in the metastatic cells compared to the non-malignant and non-metastatic cells. This suggests that different de novo lipogenesis and other specific signal transduction pathways are activated in aggressive metastatic cells as compared to normal and non-metastatic cells.

No MeSH data available.


Related in: MedlinePlus