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

Kanlayanee Sawanyawisuth, Chaisiri Wongkham, Chawalit Pairojkul, O. Tur Saeseow, Gregory J. Riggins, Norie Araki, Sopit Wongkham

Research output: Contribution to journalArticlepeer-review

Abstract

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 dependent on the amount of cellular enzyme. The present study highlights the involvement of MetAP2 in an early event of carcinogenesis of CCA. The findings represent the first description of increased MetAP2 expression in CCA. The inhibition of enzyme activity using MetAP2 inhibitors may be a potential strategy for long-term control of tumor development and progression in CCA patients.

Original languageEnglish (US)
Pages (from-to)378-385
Number of pages8
JournalActa Oncologica
Volume46
Issue number3
DOIs
StatePublished - Apr 26 2007

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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