Hiroaki Kasashima1, Masakazu Yashiro2,3, Haruhito Kinoshita1, Tatsunari Fukuoka1, Tamami Morisaki1, Go Masuda1, Katsunobu Sakurai1, Naoshi Kubo1, Masaichi Ohira1, Kosei Hirakawa1. 1. Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan. 2. 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. 3. Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka, Japan. m9312510@med.osaka-cu.ac.jp.
Abstract
PURPOSE: 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. CONCLUSION: LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.
PURPOSE: 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. CONCLUSION:LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.
Authors: A Borel; D Eichenberger; J Farjanel; E Kessler; C Gleyzal; D J Hulmes; P Sommer; B Font Journal: J Biol Chem Date: 2001-10-29 Impact factor: 5.157
Authors: Héctor Peinado; Maria Del Carmen Iglesias-de la Cruz; David Olmeda; Katalin Csiszar; Keith S K Fong; Sonia Vega; Maria Angela Nieto; Amparo Cano; Francisco Portillo Journal: EMBO J Date: 2005-08-18 Impact factor: 11.598
Authors: Christelle P El-Haibi; George W Bell; Jiangwen Zhang; Anthony Y Collmann; David Wood; Cally M Scherber; Eva Csizmadia; Odette Mariani; Cuihua Zhu; Antoine Campagne; Mehmet Toner; Sangeeta N Bhatia; Daniel Irimia; Anne Vincent-Salomon; Antoine E Karnoub Journal: Proc Natl Acad Sci U S A Date: 2012-10-02 Impact factor: 11.205
Authors: Thomas R Cox; Demelza Bird; Ann-Marie Baker; Holly E Barker; Melisa W-Y Ho; Georgina Lang; Janine T Erler Journal: Cancer Res Date: 2013-01-23 Impact factor: 12.701
Authors: Bhavani S Kowtharapu; Ruby Kala Prakasam; Radovan Murín; Dirk Koczan; Thomas Stahnke; Andreas Wree; Anselm G M Jünemann; Oliver Stachs Journal: Int J Mol Sci Date: 2018-05-09 Impact factor: 5.923