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

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.

Keywords: 67kDa laminin receptor; Cholangiocarcinoma; Lysyl oxidase-like 2; Prognosis.