The Effect Of Lysyl Oxidase-like 2 In The Invasion And Metastasis Of Cholangiocarcinoma

Metastasis is the main factor to infect the surgivcal manners selection and long term survival rate of patients with cholangiocaicinoma. Tumor cell adhension, moving and degradation of extracellular matrix is the most important step in tumor metastasis. Investing the controlling of the malig-phenotype initiating is the key point in revealing the mechanism of tumor meatstasis.Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase (LOX) protein family that consists of five members defined by highly conserved COOH-terminal sequences. Recent investigations have illustrated that the biological role of LOX extends beyond the oxidation of structuralproteins of the ECM. Indeed, several reports describe its influence on cell proliferation, intracellular signal responses, and cell migration, which reveal that it can act as an antagonist or a protagonist of malignant processes. Previous study data have shown that most tumor cells (squamous cell carcinoma in head and neck, breast carcinoma, colonic carcinoma, etc) express elevated levels of LOXL2 but not in normal tissue and the expression level of LOXL2 is directly proportional to invasion and metastasis ability of maligmant cells. Taken together, these results raise the possibility of using LOXL2 expression as an additional predictive/prognostic marker for carcinoma progression. It is speculated that LOXL2 plays the role of common regulator in malignant tumour metastasis.To test this hypothesis, we evaluated the expression pattern of LOXL2 in cholangiocarcinoma and the role of LOXL2 in the metastasis of cholangiocarcinoma. Immunohistochemistry method was used to quantify LOXL2 expression, as well as tumor metastasis associated CD44,MMP-9 in cholangiocarcinoma cells line(QBC939). The expression degree of CD44,MMP-9 in QBC939 cells was evaluated following LOXL2 expression down-regulated by Vector-mediated RNAi.The positive expression rate was observed in surgical resection cholangiocarcinoma tissues as 70.83 %(34/48) , there was no correlation between the expression of LOXL2 and such factors as sex, age of patients with cholangiocarcinoma and differentiation grade , but a significant correlation with its metastasis was found (P<0.05). After pGenesil-shLOXL2 plasmid was constructed and transfected into QBC939 cell, we examined the lower expression of LOXL2 protein by immunocytochemistry and the LOXL2 protein significantly decreased the expression of CD44,MMP-9 protein in QBC939 cells.The results demonstrate that LOXL2 overexpression is a critical molecular marker of cholangiocarcinoma and is strongly associated with invasion and metastasis of this tumor. Maybe LOXL2 overexpression is an important factor in keeping high metastatic phentotype of cholangiocarcinoma cells in vitro.LOXL2 controll cholangiocarcinoma invasion and metastasis by mediating tumor cells adnension, degradation of extracellular matrix.