Abstract 3566: Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia

Abstract

Abstract Purpose: Hypoxic environments are randomly scattered throughout carcinomas. Although hypoxia is cytotoxic to both cancer cells and normal cells, some types of cancer cells acquire characteristics that allow them to survive and progress in a hypoxic environment. Hypoxia is considered to be associated with aggressive tumor phenotypes of gastric carcinomas, including the ability to metastasize. Hypoxia is clinically associated with metastasis and poor patient outcome, however the underlying processes remain unclear. 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 siLOX on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by RT-PCR, western blot, wound-healing assay, and 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 of EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. Taken together, 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: HIF-1α might increase the expression of LOX, which affects the EMT of gastric cancer cells in hypoxic conditions via down-regulation of E-cadherin level and up-regulation of vimentin level. LOX expression may be a useful prognostic factor for patients with gastric cancer. Citation Format: Masakazu Yashiro, Hiroaki Kasashima, Yurie Yamamoto, Kenji Kuroda, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Shingo Togano, Tomohisa Okuno, Yuichiro Miki, Masaichi Ohira. Lysyl oxidase is associated with the epithelial–mesenchymal transition of gastric cancer cells in hypoxia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3566.