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Updated: May 31, 2026
08:01
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Pleural mesothelioma side populations have a precursor phenotype
Claudia Frei1, Isabelle Opitz, Alex Soltermann
1Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, Haeldeliweg 4, 8044 Zurich, Switzerland.
Carcinogenesis
|July 7, 2011
Summary
Malignant pleural mesothelioma (MPM) side population (SP) cells exhibit chemoresistance and self-renewal, potentially driving tumor recurrence after chemotherapy. Targeting these SP cells may offer new therapeutic strategies for MPM.
Area of Science:
- Oncology
- Cancer Biology
- Cell Biology
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- Tumor recurrence after chemotherapy suggests the presence of chemoresistant cancer stem cells.
- Identifying these resistant subpopulations is crucial for developing effective therapies.
Purpose of the Study:
- To identify chemoresistant subpopulations within MPM using a side population (SP) functional assay.
- To investigate the self-renewal, chemoresistance, and tumorigenicity of SP versus non-side population (NSP) cells.
- To characterize the phenotype of SP cells and their potential role in tumor recurrence.
Main Methods:
- DyeCycleViolet staining to establish the SP assay for identifying chemoresistant MPM cells.
- Assays for self-renewal, chemoresistance, and tumorigenicity in SP and NSP fractions.
- Immunohistochemical characterization of tumors (mesothelin, calretinin, N-cadherin, D2-40, WT1) and flow cytometry for stem cell markers (CD90, CD73, CD105).
Main Results:
- SP cells in MPM demonstrated self-renewal properties and enhanced chemoresistance compared to NSP cells.
- Tumors derived from SP cells showed a mesothelium precursor phenotype (WT1 negative, cytoplasmic D2-40 positive) and increased tumorigenicity.
- SP cells were enriched for CD105 negative/low expression, smaller size, and higher tumorigenicity, mirroring phenotypic shifts in relapsed tumors post-chemotherapy.
Conclusions:
- Chemoresistant, small-sized, CD105 negative/low SP cells in MPM are implicated as the cellular source of tumor recurrence.
- These SP cells possess self-renewal and chemoresistance capabilities, suggesting they function as cancer stem cells.
- Further research into the mechanisms of chemoresistance and self-renewal in this subpopulation could identify novel therapeutic targets for MPM.
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