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Updated: Jun 8, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Mesothelin as a potential therapeutic target in human cholangiocarcinoma
Liping Yu1, Mingqian Feng, Heungnam Kim
11. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
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 specimens and 3 of 6 CCA cell lines (OZ, KMBC and KMCH). No mesothelin 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 IC(50) 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.
Insights
Mesothelin is overexpressed in a third of cholangiocarcinoma (CCA) cases, making it a promising target for immunotherapy. The SS1P immunotoxin demonstrated significant growth inhibition in mesothelin-expressing CCA cells, suggesting potential therapeutic applications.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are primary liver cancers with limited therapeutic options.
- Mesothelin is an emerging therapeutic target in various cancers.
- This study investigates mesothelin expression in liver cancer for potential immunotherapy.
Purpose of the Study:
- To determine mesothelin expression levels in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA).
- To evaluate the potential of mesothelin as a therapeutic target for immunotherapy in liver cancer.
Main Methods:
- Immunohistochemistry was used to assess mesothelin expression in HCC and CCA specimens.
- Protein expression was further analyzed by immunoblotting and flow cytometry.
- The SS1P immunotoxin was tested against CCA cell lines expressing mesothelin.
Main Results:
- Mesothelin was strongly expressed in 33% of CCA specimens and 3 of 6 CCA cell lines, but not in HCC or normal liver tissue.
- High mesothelin expression was observed in 22% of CCA specimens, comparable to cell line models.
- SS1P exhibited potent and specific growth inhibition of mesothelin-positive CCA cells in vitro.
Conclusions:
- Mesothelin is overexpressed in approximately one-third of CCA tissues.
- The SS1P immunotoxin shows significant single-agent activity against CCA in vitro.
- These findings support the potential of SS1P for immunotherapeutic treatment of CCA.
