title: Sphingosine-1-phosphate/sphingosine kinase 1-dependent lymph node metastasis in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  To establish whether Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SphK1) contribute to lymph node metastasis in esophageal squamous cell carcinoma.
  
  
  METHODS
  Immunohistochemical analysis of SphK1 expression was performed using a tissue microarray containing 177 thoracic squamous cell esophageal cancer specimens resected at surgery, to investigate the association between intratumoral SphK1 expression and lymph node metastasis. Serum S1P levels and intratumoral SphK1 mRNA and protein expression were also evaluated in mice with vs. mice without lymph node metastasis in a murine lymph node metastasis model.
  
  
  RESULTS
  Among 177 esophageal cancer patients, 127 (72%) were defined as being SphK1-positive. In univariate and multivariate analyses, SphK1 expression status was a significant factor contributing to lymph node metastasis and poorer 5-year overall survival. In the murine lymph node metastasis model, there was no difference in tumor volume or weight between the lymph node metastasis-negative and lymph node metastasis-positive groups. However, levels of SphK1 mRNA and protein and serum S1P levels were all much higher in the metastasis-positive group.
  
  
  CONCLUSIONS
  S1P/SphK1 may be novel targets for inhibiting lymph node metastasis in esophageal squamous cell carcinoma, and may provide the basis for a therapeutic strategy to suppress lymph node metastasis.
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kawakita
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. motoyama@doc.med.akita-u.ac.jp.|Department of Comprehensive Cancer Control, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan. motoyama@doc.med.akita-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Bioscience Education and Research Support Center, Akita University School of Medicine, Akita, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Koyota
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Wakita
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of General Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
mesh_terms: D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D008246:Lysophospholipids / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate
keywords: Esophageal cancer; Lymph node metastasis; Sphingosine kinase 1; Sphingosine-1-phosphate; Squamous cell carcinoma