title: Matrix-assisted laser desorption/ionization mass spectrometry imaging of cell cultures for the lipidomic analysis of potential lipid markers in human breast cancer invasion.
abstract: BACKGROUND
  Breast cancer is the leading cause of cancer death among women worldwide. Identification of lipid targets that play a role in breast cancer invasion may advance our understanding of the rapid progression of cancer and may lead to the development of new biomarkers for the disease.
  
  
  METHODS
  Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied for the lipidomic profiling of two poorly invasive and two highly invasive breast cancer cell lines to identify the differentially accumulated lipids related to the invasive phenotype. The four cell lines were individually grown on indium tin oxide (ITO)-coated glass slides, analyzed as cell cultures. The raster width and matrix for detection were optimized to improve detection sensitivity.
  
  
  RESULTS
  Optimized MSI measurements were performed directly on the cell culture with 9-aminoacridine as matrix, resulting in 215 endogenous compounds detected in positive ion mode and 267 endogenous compounds in negative ion mode in all the four cell lines, representing the largest group of analytes that have been analyzed from cells by a single MSI study. In highly invasive cell lines, 31 lipids including phosphatidylglycerol (PG) and phosphatidic acids were found upregulated and eight lipids including sphingomyelin (SM) downregulated in negative ion mode. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, like oleic-acid-containing PG, may be involved in mitochondrial dysfunction and thus affect the invasion of breast cancer cells. The deficiency of SM may be related to the disruption of apoptosis in highly invasive cancer cells.
  
  
  CONCLUSIONS
  This work uncovered more analytes in cells by MSI than previous reports, providing a better visualization and novel insights to advance our understanding of the relationship between rapid progression of breast cancer and lipid metabolism. The most altered lipids may aid the discovery of diagnostic markers and therapeutic targets of breast cancer.
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, China.
authors.forename: Hemi
authors.initials: H
authors.lastname: Luan
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, China.
authors.forename: Shuhai
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|Key Laboratory of Metabolomics at Shenzhen, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China.|School of Medicine, Tsinghua University, Beijing, 10084, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D008055:Lipids