Methionine aminopeptidase 2 over-expressed in cholangiocarcinoma: Potential for drug target

Methionine aminopeptidases (MetAP) are proteases which remove the N-terminal methionine from newly synthesized proteins. Associations of MetAP2 with tumor progression of different cancers have been repeatedly reported. We aim to determine if MetAP2 is expressed in cholangiocarcinomas (CCA) and investigate to see if it would be a useful therapeutic target. We evaluated MetAP2 expression by immunohistochemistry in 82 patients of intrahepatic CCA. MetAP2 was expressed in bile ducts to various degrees. It was occasionally expressed with weak staining in normal bile duct epithelium but was strikingly over-expressed in dysplastic bile duct epithelia, primary and metastatic CCA tissues (p < 0.001). The increased expression of MetAP2 in proliferating bile duct was evident. All metastatic tumors had stronger expression of MetAP2 than the corresponding primary tumors. Fumagillin, a MetAP2 specific inhibitor, significantly inhibited cell proliferation in dose dependent manner and the degree of growth inhibition was ...