DDR1 enhances invasion and metastasis of gastric cancer via epithelial-mesenchymal transition
DDR1 enhances invasion and metastasis of gastric cancer via epithelial-mesenchymal transition
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DDR1通过上皮间质转化增强胃癌的侵袭和转移
DOI：
10.1007/s13277-016-5070-6
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发表时间：
2016-09-01
期刊：
影响因子：
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通讯作者：
Zhang, Dekui
中科院分区：
文献类型：
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作者：
Xie, Ruixia;Wang, Xiaoying;Zhang, Dekui
本研究旨在探讨DDR 1在胃癌细胞中通过上皮间质转化（EMT）途径对胃癌侵袭转移的影响。采用免疫组化法检测胃癌组织中DDR 1、E-cadherin、Vimentin的表达，以及胃癌细胞株和正常胃上皮细胞中DDR 1的表达。通过下调和上调DDR 1并检测EMT相关蛋白表达和生物学特性的相应变化，探讨了DDR 1表达与胃癌细胞系EMT之间的关系。此外，建立了稳定转染DDR 1基因的胃癌细胞裸鼠移植瘤模型，进一步研究DDR 1基因表达对胃癌细胞形态和生长的影响。结果表明，DDR 1在胃癌组织和胃癌细胞系中的表达高于癌旁组织和正常细胞系，且在分化较差的胃癌中表达明显增高（P < 0.01），壁浸润深度提前（p = 0.020）、淋巴结转移（p = 0.0001）、肝转移（p < 0.01）和高TNM分期（p < 0.01）。Western blot分析显示，DDR 1过表达导致E-cadherin表达显著降低（p < 0.01），Vimentin和Snail表达显著增加（p < 0.01），而DDR 1敲低则导致相反的结果。DDR 1过表达促进胃癌细胞增殖（p < 0.05）、迁移（p < 0.01）和侵袭（p < 0.01），促进裸鼠移植瘤生长（p < 0.05）和微血管形成（p < 0.01）。我们的研究证实DDR 1通过EMT促进胃癌的侵袭和转移。
In this study, we investigated the effects of DDR1 on the invasion and metastasis in gastric cancer (GC) via epithelial-mesenchymal transition (EMT). Immunohistochemistry analysis was used to detect DDR1, E-cadherin, and Vimentin expression in GC tissues as well as DDR1 expression in GC cell lines and normal gastric epithelial cells. The relationship between DDR1 expression and EMT in GC cell lines was explored by down and upregulating DDR1 and examining corresponding changes in the expression of EMT-related proteins and in biological characteristics. Furthermore, a nude mice model with a transplantation tumor generating from stably transfected GC cells with DDR1 overexpression was established and performed to further reveal the effects of DDR1 expression on cellular morphology and growth of GC. Our results showed that DDR1 was highly expressed in GC tissues and cell lines compared with adjacent tissues and normal cell line, and its expression was significantly higher in GC having poor differentiation (p < 0.01), advanced depth of wall invasion (p = 0.020), lymph node metastasis (p = 0.0001), liver metastasis (p < 0.01), and high TNM stage (p < 0.01). Western blot analyses revealed that DDR1 overexpression resulted in a significant decrease in the expression of E-cadherin (p < 0.01) and an increase in the expression of Vimentin and Snail (p < 0.01), while knockdown of DDR1 led to opposite outcomes. We further demonstrated that DDR1 overexpression promoted GC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01), and accelerated the growth (p < 0.05) as well as the microvessel formation (p < 0.01) of transplantation tumor in nude mice. Our study establishes that DDR1 enhances invasion and metastasis of gastric cancer via EMT.