title: Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia.
abstract: OBJECTIVE
  It has been reported that lysyl oxidase (LOX) is a hypoxia-responsive factor and is associated with the malignant progression of carcinoma. The aim of this study was to clarify the relationship between the epithelial-mesenchymal transition (EMT) and LOX in gastric cancer cells under hypoxia.
  
  
  METHODS
  Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12, were used in an in vitro study. The effect of LOX small interfering RNA (siRNA) on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by reverse transcription PCR, Western blot, a wound-healing assay, and an invasion assay. Correlations between LOX expression and the clinicopathological features of 544 patients with gastric carcinoma were examined immunohistochemically.
  
  
  RESULTS
  Hypoxic conditions increased the number of polygonal or spindle-shaped cells resulting from EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. The number of migrating and invading gastric cancer cells in hypoxia was significantly decreased by LOX knockdown. LOX siRNA significantly increased the E-cadherin level and decreased the vimentin level of gastric cancer cells. LOX expression was significantly associated with invasion depth, tumor differentiation, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal metastasis. Multivariable analysis revealed that LOX was an independent parameter for overall survival.
  
  
  CONCLUSIONS
  LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kasashima
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. m9312510@med.osaka-cu.ac.jp.|Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka, Japan. m9312510@med.osaka-cu.ac.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Haruhito
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Tatsunari
authors.initials: T
authors.lastname: Fukuoka
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Morisaki
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Masuda
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Sakurai
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kubo
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000368:Aged; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000072258:Tumor Hypoxia
chemical_list: D015820:Cadherins; D008249:Protein-Lysine 6-Oxidase
keywords: Epithelial–mesenchymal transition; Gastric cancer; Lysyl oxidase