Mesothelin as a potential therapeutic target in human cholangiocarcinoma

Liping Yu, Mingqian Feng, Heungnam Kim, Yen Phung, David E. Kleiner, Gregory J. Gores, Min Qian, Xin Wei Wang, Mitchell Ho

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common primary liver cancers, yet there have been no significant advances in effective therapeutics. Mesothelin has been reported as a new therapeutic target in various types of cancer. Here, we investigated the expression of mesothelin in liver cancer and its potential role as a novel therapeutic target for immunotherapy. Methods: HCC and CCA specimens were examined by immunohistochemistry for mesothelin expression. Protein expression was assessed by immunoblotting and flow cytometry. The SS1P immunotoxin targeting mesothelin was evaluated in the well-established CCA cell lines HuCCT1, HuH-28, KMBC, KMCH, Mz-ChA-1 and OZ. Results: We showed strong immunochemical mesothelin staining in 33% of the surgically resected CCA speci mens and 3 of 6 CCA cell li nes (OZ, KMBC and KMCH). No mesotheli n staining was found in HCC or normal liver tissue. Mesothelin was primarily localized to the cellular plasma membrane and the mature form (molecular weight, ~40 kDa) was expressed at a high level in CCA tissues. Moreover, 22% of CCA specimens had a high mesothelin expression level which was comparable to the CCA cell line models. Interestingly, SS1P showed very high and specific growth inhibition when added to mesothelin-expressing CCA cells with IC50 values ranging from 0.5 to 11 ng/mL. Conclusions: Mesothelin is overexpressed in one-third of CCA tissues. SS1P targeting mesothelin reveals a remarkable single agent activity against CCA in vitro. These findings indicate a potential for SS1P in the immunotherapeutic treatment of CCA.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalJournal of Cancer
Volume1
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Bile duct carcinoma
  • Cholangiocarcinoma
  • Hepatocellular carcinoma
  • Immunotoxin
  • Mesothelin
  • SS1P

ASJC Scopus subject areas

  • Oncology

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    Yu, L., Feng, M., Kim, H., Phung, Y., Kleiner, D. E., Gores, G. J., Qian, M., Wang, X. W., & Ho, M. (2010). Mesothelin as a potential therapeutic target in human cholangiocarcinoma. Journal of Cancer, 1(1), 141-149. https://doi.org/10.7150/jca.1.141