title: Comparative Metabolomic and Lipidomic Analysis of Phenotype Stratified Prostate Cells.
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.
authors.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.
authors.forename: Tanya C
authors.initials: TC
authors.lastname: Burch
authors.affiliation: Waters Corporation, Milford, Massachusetts, United States of America.
authors.forename: Giorgis
authors.initials: G
authors.lastname: Isaac
authors.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.
authors.forename: Christiana L
authors.initials: CL
authors.lastname: Booher
authors.affiliation: Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Johng S
authors.initials: JS
authors.lastname: Rhim
authors.affiliation: Waters Corporation, Milford, Massachusetts, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Rainville
authors.affiliation: Waters Corporation, Manchester, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Langridge
authors.affiliation: Waters Corporation, Milford, Massachusetts, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Baker
authors.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.
authors.forename: Julius O
authors.initials: JO
authors.lastname: Nyalwidhe
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002797:Choline Kinase / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007295:Inositol Phosphates / Q000032:analysis; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010641:Phenotype; D010713:Phosphatidylcholines / Q000032:analysis; D010714:Phosphatidylethanolamines / Q000032:analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D059467:Transcriptome / Q000235:genetics
chemical_list: D007295:Inositol Phosphates; D008055:Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C014575:glycerylphosphoinositol; C517212:CHKA protein, human; D002797:Choline Kinase