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 language | English (US) |
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Pages (from-to) | 141-149 |
Number of pages | 9 |
Journal | Journal of Cancer |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - 2010 |
Keywords
- Bile duct carcinoma
- Cholangiocarcinoma
- Hepatocellular carcinoma
- Immunotoxin
- Mesothelin
- SS1P
ASJC Scopus subject areas
- Oncology