Gao Minna, Zhang Xiong, Li Dan, He Ping, Tian Wenguang, Zeng Bo
Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Oncotarget. 2016 Dec 20;7(51):85502-85514. doi: 10.18632/oncotarget.13453.
The underlying mechanisms of colorectal carcinoma (CRC) metastasis remain to be elucidated. The aim of this study is to investigate clinical significance and the expression of eIF4E, VEGF-C, MMP-2, and E-cadherin in the CRC metastasis. We investigated their expressions in 108 patients, analyzed the relationships between their expressions in CRC and evaluated the relationships between their expressions and clinical pathogenic parameters. Furthermore, their roles in patient survival and in CRC metastasis were also investigated. We found that eIF4E, VEGF-C and MMP-2 were up-regulated in CRC, and their expression frequencies (EFs) were higher in cancerous tissues than in adjacent normal tissues. The EF of E-cadherin is lower in cancerous tissues than in adjacent normal tissues. Totally, their EFs were not associated with sex and age of patient, however, their EFs were associated with tumor differentiation, the depth of invasion, lymph node metastasis and tumor stages. Furthermore, eIF4E, VEGF-C, and MMP-2 shortened and E-cadherin prolonged survival in patient-derived CRC xenografts. Similarly, eIF4E, VEGF-C, and MMP-2 promoted and E-cadherin suppressed the lung metastasis of CRC cells. In addition, knockdown of eIF4E inhibited migration of CRC cells, downregulated VEGF-C, MMP-2 and upregulated E-cadherin. In conclusion, eIF4E promoted CRC metastasis via up-regulating the expression of VEGF-C, MMP-2 and suppressing E-cadherin.
结直肠癌(CRC)转移的潜在机制仍有待阐明。本研究旨在探讨真核生物翻译起始因子4E(eIF4E)、血管内皮生长因子C(VEGF-C)、基质金属蛋白酶2(MMP-2)和E-钙黏蛋白在CRC转移中的临床意义及表达情况。我们研究了它们在108例患者中的表达,分析了它们在CRC中的表达之间的关系,并评估了它们的表达与临床病理参数之间的关系。此外,还研究了它们在患者生存及CRC转移中的作用。我们发现,eIF4E、VEGF-C和MMP-2在CRC中上调,其表达频率(EFs)在癌组织中高于相邻正常组织。E-钙黏蛋白的EF在癌组织中低于相邻正常组织。总体而言,它们的EFs与患者的性别和年龄无关,然而它们的EFs与肿瘤分化、浸润深度、淋巴结转移和肿瘤分期相关。此外,在源自患者的CRC异种移植中,eIF4E、VEGF-C和MMP-2缩短了生存时间,而E-钙黏蛋白延长了生存时间。同样,eIF4E、VEGF-C和MMP-2促进了CRC细胞的肺转移,而E-钙黏蛋白则抑制了肺转移。此外,敲低eIF4E可抑制CRC细胞的迁移,下调VEGF-C、MMP-2并上调E-钙黏蛋白。总之,eIF4E通过上调VEGF-C、MMP-2的表达及抑制E-钙黏蛋白促进了CRC转移。