title: NMR metabolomics of MTLn3E breast cancer cells identifies a role for CXCR4 in lipid and choline regulation.
abstract: The alpha chemokine receptor CXCR4 is up-regulated in certain types of breast cancer. Truncation of the C-terminus of this receptor alters cell morphology and increases invasiveness and metastatic potential. Here, to better understand the effects of CXCR4 expression and truncation in breast cancer cells, we have used high resolution magic angle spinning (HR-MAS) NMR studies of rat breast carcinoma MtLn3E cells to characterize the metabolite complement of cells heterologously expressing human CXCR4 or its C-terminal truncation mutant, Δ34-CXCR4. Notable reductions in choline levels were detected when either cells expressing wild-type CXCR4 or Δ34-CXCR4 were compared with cells containing an empty expression vector. Cells expressing CXCR4-Δ34 had reduced lipid content when compared with either the wild-type CXCR4 expressing cells or those containing the empty expression vector. Taken together, our results show that distinct effects on the metabolite complement can be linked to either CXCR4 expression or CXCR4 regulation. The metabolite markers for these two effects identified in the present study can, in turn, be used to further investigate the role of CXCR4 in metastasis.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. louic.vermeer@kcl.ac.uk
authors.forename: Louic S
authors.initials: LS
authors.lastname: Vermeer
authors.forename: Gilbert O
authors.initials: GO
authors.lastname: Fruhwirth
authors.forename: Pahini
authors.initials: P
authors.lastname: Pandya
authors.forename: Tony
authors.initials: T
authors.lastname: Ng
authors.forename: A James
authors.initials: AJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism*; D003001:Cloning, Molecular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins; D002794:Choline