赖氨酰氧化酶
间质细胞
癌症研究
癌相关成纤维细胞
癌症
癌细胞
成纤维细胞
生物
病理
转移
成纤维细胞活化蛋白
细胞培养
医学
内科学
细胞外基质
细胞生物学
遗传学
作者
Hiroaki Kasashima,Masakazu Yashiro,Haruhito Kinoshita,Tatsunari Fukuoka,Tamami Morisaki,Go Masuda,Katsunobu Sakurai,Naoshi Kubo,Masaichi Ohira,Kosei Hirakawa
出处
期刊:Cancer Letters
[Elsevier]
日期:2014-11-01
卷期号:354 (2): 438-446
被引量:70
标识
DOI:10.1016/j.canlet.2014.08.014
摘要
The aim of this study was to clarify the role of fibroblast-derived Lysyl oxidase-like 2 (LOXL2) in the development of gastric cancer. The correlation between the clinicopathological features of 548 primary gastric carcinomas and LOXL2 expression in stromal cells was examined by immunohistochemistry. Two gastric cancer cell lines, OCUM-12 and NUGC-3, and cancer-associated fibroblasts (CAFs) were used in this in vitro study. The effect of fibroblast-derived LOXL2 on the motility of gastric cancer cells was analyzed by using a wound-healing assay, a double-chamber invasion assay, and western blot. LOXL2 expression in stromal cells was significantly associated with tumor invasion depth, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination. Multivariable logistic regression analysis revealed that LOXL2 expression in stromal cells could be an independent predictive parameter for the overall survival of patients. CAFs significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells. This motility-stimulating ability of CAFs was inhibited by LOXL2 siRNA. Western blot analysis indicated that phosphorylation of focal adhesion kinase (FAK) in cancer cells was increased by the conditioned medium from CAFs, and was decreased by the conditioned medium from LOXL2 siRNA-treated CAFs. LOXL2 expression in stromal cells may be a useful prognostic factor for patients with gastric cancer. Fibroblast-derived LOXL2 may stimulate the motility of gastric cancer cells.
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