The Effect Of Eukaryotic Protein Synthesis Initiation Factor 4E In The Modulation Of The Invasion And Metastasis Of Cholangiocarcinoma

Metastasis is the main factor to infect the surgical manners selection and long term survival rate of patients with cholangiocaicinoma. Tumor cell adhension, moving and angiogenesis is the most important step in tumor metastasis. Investiging the triggering and controlling of the malig-phenotype initiating is the key point in revealing the mechanism of tumor meatstasis. Eukaryotic initiation factor 4E (eIF4E) is a 25-kDa cap binding protein that plays an important role in the initiation of protein synthesis. Previous study data have shown that most tumor cells(squamous cell carcinoma in head and neck, pulmonary carcinoma, breast carcinoma, colonic carcinoma, etc) express elevated levels of eIF4E but not in normal tissue and the expression level of eIF4E is directly proportional to invasion and metastasis ability of maligmant cells. It is speculated that eIF4E plays the role of common regulator in malignant tumour metastasis. The present study has been carried out to investigate the role of eIF4E cholangiocarcinoma metastasis. Immunohistochemistry method Western blot analysis was used to quantify eIF4E expression, as well as tumor metastasis associated CD44,MMP-9,VEGF in surgical resection cholangiocarcinoma tissues and cholangiocarcinoma cells(QBC939). The expression degree of CD44,MMP-9,VEGF in QBC939 cells was evaluated following eIF4E expression down-regulated by antisense olionucleotides transfection method. The data showed that the degree of eIF4E expression is up-regulated in surgical resection cholangiocarcinoma tissues and cholangiocarcinoma cells (QBC939). The overexpression of eIF4E is independent of patients age, sex and tumor grade but is strongly dependent of tumour cells differentiation. The degree of eIF4E overexpression was strongly correlated with the degree of CD44,MMP-9,VEGF expression in cholangiocarcinoma tissues. Cholangiocarcinoma cells (QBC939) with higher metastasis ability expressed higher levels of eIF4E compared to that with relatively lower metastasis ability. Cholangiocarcinoma cells (QBC939) transfected with antisense oligonucleotides expressed significantly lower degree of eIF4E but no significant difference emerged between sense oligonucleotides transfected cells QBC939 cells and normal QBC939 cells. The expression degree of CD44,MMP-9 and VEGF in QBC939 cells decreased significantly following eIF4E expression down regulated by antisense oligonucleotides transfection. The results demonstrates that eIF4E overexpression is a critical molecular marker of cholangiocarcinoma and is strongly associated with invasion and metastasis of this tumor. Maybe eIF4E overexpression is an important factor in keeping high metastatic phentotype of cholangiocarcinoma cells in vitro. eIF4E controll cholangiocarcinoma invasion and metastasis by mediating tumor cells adnension, degradation of extracellular matrix and angiogenesis.