67层粘连蛋白受体通过上调胆管癌中赖氨酰氧化酶样2的表达促进肿瘤细胞的恶性潜能。

67 laminin receptor promotes the malignant potential of tumour cells up-regulating lysyl oxidase-like 2 expression in cholangiocarcinoma.

作者信息

Xu Jing, Li Dajing, Li Xiaowu, Liu Zipei, Li Tianyu, Jiang Peng, He Qiang, Tian Feng, Gao Yang, Wang Dechun, Wang Shuguang

机构信息

Hepatobiliary Surgery Institute, Laboratory of Liver Transplantation, Southwest Hospital, Third Military Medical University, Chongqing, PR China; Hepatobiliary Surgery Department, First People Hospital of Yunnan Province, Kunming University of Science and Technology, PR China.

Hepatobiliary Surgery Institute, Laboratory of Liver Transplantation, Southwest Hospital, Third Military Medical University, Chongqing, PR China.

出版信息

Dig Liver Dis. 2014 Aug;46(8):750-7. doi: 10.1016/j.dld.2014.03.017. Epub 2014 May 1.

DOI:10.1016/j.dld.2014.03.017

PMID:24794791

Abstract

BACKGROUND

67 laminin receptor (67LR) plays an important role in the invasion and metastasis of cholangiocarcinoma, but its mechanism remains unclear.

AIMS

We investigated the clinical significance of 67LR and its relation to lysyl oxidase-like 2 (LOXL2) in 67LR-mediated invasion and metastasis in cholangiocarcinoma.

METHODS

The clinical significance of 67LR and LOXL2 expression and the prognosis of patients were investigated in 73 cancerous and 32 paracancerous tissues by immunohistochemistry. The impact of LOXL2 on invasion, metastasis and 67LR expression was evaluated in cholangiocarcinoma cells by shRNA or expressed-plasmid transfection.

RESULTS

Expression of 67LR was recognized in 35.62% cholangiocarcinoma tissue, and none in paracancerous tissues. LOXL2 was positively correlated with expression of 67LR. Expression of 67LR or LOXL2 in cholangiocarcinomas was significantly associated with lymph node metastasis, differentiation and poor overall survival. Cox analysis showed that 67LR can act as an independent prognostic biomarker of prognosis in cholangiocarcinoma patients. Expression of LOXL2 decreased by knockdown of 67LR and increased by overexpression of 67LR in cholangiocarcinoma cells. Knockdown of LOXL2 reduced invasion and metastasis in vitro and in vivo.

CONCLUSION

67LR may regulate the expression of LOXL2 to promote invasion and metastasis in cholangiocarcinoma cells. It could be used as an independent prognostic marker in cholangiocarcinoma patients.

摘要

背景

67层粘连蛋白受体（67LR）在胆管癌的侵袭和转移中起重要作用，但其机制尚不清楚。

目的

我们研究了67LR的临床意义及其在胆管癌67LR介导的侵袭和转移中与赖氨酰氧化酶样2（LOXL2）的关系。

方法

通过免疫组织化学研究73例癌组织和32例癌旁组织中67LR和LOXL2表达的临床意义及患者的预后。通过短发夹RNA（shRNA）或表达质粒转染评估LOXL2对胆管癌细胞侵袭、转移和67LR表达的影响。

结果

35.62%的胆管癌组织中可检测到67LR表达，癌旁组织中均未检测到。LOXL2与67LR的表达呈正相关。胆管癌中67LR或LOXL2的表达与淋巴结转移、分化程度及总体生存率差显著相关。Cox分析表明，67LR可作为胆管癌患者预后的独立预后生物标志物。在胆管癌细胞中，敲低67LR可使LOXL2表达降低，过表达67LR可使LOXL2表达增加。敲低LOXL2可在体外和体内减少侵袭和转移。