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Updated: May 7, 2026

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells
Simon A Fox1, Alex K Richards, Ivonne Kusumah
1Molecular Pharmacology Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia.
Abstract:
Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.
Insights
Altered Wnt signaling molecules are found in malignant mesothelioma (MM), an aggressive cancer. Targeting Wnt/β-catenin pathways may offer new treatments for MM proliferation and drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure.
- The role of Wnt signaling in MM has not been extensively studied.
- Current treatments for MM remain a significant clinical challenge.
Purpose of the Study:
- To investigate the expression of Wnt signaling pathway components in MM.
- To determine the functional impact of Wnt signaling on MM cell behavior.
- To explore therapeutic strategies targeting the Wnt pathway in MM.
Main Methods:
- Surveyed Wnt pathway molecule expression in MM cell lines and primary mesothelial cells.
- Assessed MM cell response to exogenous Wnt ligands and inhibitors.
- Investigated the effect of targeting β-catenin on MM cell sensitivity to chemotherapy.
Main Results:
- Frequent expression of Wnt3 and Wnt5a, and Fzd 2, 4, 6 observed.
- Downregulation of Wnt4, Fzd3, sFRP4, APC, and axin2 in MM cells compared to mesothelial cells.
- Wnt3a promoted MM proliferation, sFRP4 inhibited it, and targeting β-catenin sensitized MM cells to cytotoxic drugs.
Conclusions:
- Evidence of altered Wnt/Fzd signaling molecule expression in MM.
- Wnt pathway modulation presents a potential therapeutic avenue for MM.
- Targeting Wnt signaling may overcome proliferation and drug resistance in malignant mesothelioma.
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