title: Analysis of breast cancer-associated glycosphingolipids using electrospray ionization-linear ion trap quadrupole mass spectrometry.
abstract: Abnormal glycosphingolipids (GSLs) are expressed in many human tumors. These tumor-associated GSLs may have important roles in tumor progression. However, they are hard to be detected because of their low concentration and the limited availability of antibodies and lectins that recognize them. Thus, mass spectrometry is an effective method to analyze GSLs with high sensitivity. Here, we use electrospray ionization-linear ion trap quadrupole mass spectrometry (ESI-LTQ-MS) and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) to determine the structure of a certain GSL in human breast cancer tissue. To obtain the breast cancer-associated GSLs, we applied relative abundance contrast of GSLs and signal-to-noise ratio (SNR) analyses. We also used α1,2 fucosidase and fucosyltransferases as tools in the structural analysis. Based on this analysis, we identified the ion with m/z 1184 molecular ion as fucosyl-lactoceramide (Fuc-LacCer) with a C16 fatty acid ceramide. Quantitative analysis of GSLs revealed both Fuc-LacCer and Globo-H increased in breast cancer tissues. However, these two breast cancer-associated GSLs had different roles. The results of SNR analysis suggested the abnormal Fuc-LacCer is specific to breast cancer. The GSL profiling of breast cancer cells showed fucosyltransferase 1 contributed to the biosynthesis of Globo-H and Fuc-LacCer. In conclusion, MS analysis identified an accumulation of Fuc-LacCer in breast cancer tissue. Our findings provide GSL profiles of human breast cancer and develop an MS method for the study of cancer-associated GSLs.
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China.
authors.forename: Biyan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Linling
authors.initials: L
authors.lastname: Ju
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Science, Peking University, Beijing 100871, China.
authors.forename: Xinshan
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Melanoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institutes of Biology and Medical Sciences, Jiangsu Laboratory of Infection Immunity, Soochow University, 199 Ren-Ai Road, Suzhou 215123, China. Electronic address: yunsenli@suda.edu.cn.
authors.forename: Yunsen
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005647:Fucosyltransferases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006028:Glycosphingolipids; D005647:Fucosyltransferases
keywords: Breast cancer; Fucosyl-lactoceramide; Fucosyltransferases; Glycosphingolipids; Mass spectrometry