title: High levels of sphingolipids in human breast cancer.
abstract: Sphingolipids, including sphingosine-1-phosphate (S1P) and ceramide, have emerged as key regulatory molecules that control various aspects of cell growth and proliferation in cancer. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients have yet to be determined. The aims of this study were to determine the levels of sphingolipids including S1P, ceramides, and other sphingolipids, in breast cancer and normal breast tissue and to compare the difference in levels of each sphingolipid between the two tissues.
  
  
  
  Tumor and noncancerous breast tissue were obtained from 12 patients with breast cancer. Sphingolipids including S1P, ceramides, and their metabolites of sphingosine, sphingomyelin, and monohexosylceramide were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry.
  
  
  
  The levels of S1P, ceramides, and other sphingolipids in the tumor were significantly higher than those in normal breast tissue. There was a relatively strong correlation in the levels of S1P between the tumor and those of normal breast tissue from the same person. On the other hand, there was no correlation in the levels of most of the ceramide species between the tumor and those of normal breast tissue from the same person.
  
  
  
  To our knowledge, this is the first study to reveal that levels of sphingolipids in cancer tissue are generally higher than those of normal breast tissue in patients with breast cancer. The correlation of S1P levels in these tissues implicates the role of S1P in interaction between cancer and the tumor microenvironment.
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan. Electronic address: mnagahashi@med.niigata-u.ac.jp.
authors: Masayuki
authors: M
authors: Nagahashi
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
authors: Junko
authors: J
authors: Tsuchida
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
authors: Kazuki
authors: K
authors: Moro
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
authors: Miki
authors: M
authors: Hasegawa
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
authors: Kumiko
authors: K
authors: Tatsuda
authors: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
authors: Ingrid A
authors: IA
authors: Woelfel
authors: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, Virginia.
authors: Kazuaki
authors: K
authors: Takabe
authors: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Japan.
authors: Toshifumi
authors: T
authors: Wakai
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Breast cancer; Ceramides; Sphingosine-1-phosphate; Tumor microenvironment