ArticleBMC cancer2014
Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) phenotype and sphere-forming capacity.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Epithelial‑mesenchymal plasticity and cisplatin resistance in germ cell tumors: Mechanisms and emerging therapeutic strategies (Review).International journal of oncology · 2025Review
- An Overview of Cellular and Molecular Determinants Regulating Chemoresistance in Pleural Mesothelioma.Cancers · 2025Review
- Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.Current medicinal chemistry · 2025Review
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Development of substituted benzimidazoles as inhibitors of human aldehyde dehydrogenase 1A isoenzymes.Chemico-biological interactions · 2024Article
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- KDM5D Histone Demethylase Identifies Platinum-Tolerant Head and Neck Cancer Cells Vulnerable to Mitotic Catastrophe.International journal of molecular sciences · 2023Article
- Review
- Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma-A 3-D In Vitro Study.International journal of molecular sciences · 2022Article
- Forchlorfenuron and Novel Analogs Cause Cytotoxic Effects in Untreated and Cisplatin-Resistant Malignant Mesothelioma-Derived Cells.International journal of molecular sciences · 2022Article
- Butein-instigated miR-186-5p-dependent modulation of TWIST1 affects resistance to cisplatin and bioenergetics of Malignant Pleural Mesothelioma cells.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance.Frontiers in medicine · 2022Review
- Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids.Oncotarget · 2021Article
- Review
- Insights into Intra-Tumoral Heterogeneity: Transcriptional Profiling of Chemoresistant MPM Cell Subpopulations Reveals Involvement of NFkB and DNA Repair Pathways and Contributes a Prognostic Signature.International journal of molecular sciences · 2021Article
- Arachidonic acid drives adaptive responses to chemotherapy-induced stress in malignant mesothelioma.Journal of experimental & clinical cancer research : CR · 2021Article
- Exploitation of the vitamin A/retinoic acid axis depletes ALDH1-positive cancer stem cells and re-sensitises resistant non-small cell lung cancer cells to cisplatin.Translational oncology · 2021Article
- Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.European journal of medicinal chemistry · 2021Article
- Tumor-associated macrophage-derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma.Cancer science · 2020Observational
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConventional chemotherapy in malignant pleural mesothelioma (MPM) has minimal impact on patient survival due to the supposed chemoresistance of cancer stem cells (CSCs). We sought to identify a sub-population of chemoresistant cells by using putative CSC markers, aldehyde dehydrogenase (ALDH) and CD44 in three MPM cell lines; H28, H2052 and Meso4.
methodsThe Aldefluor assay was used to measure ALDH activity and sort ALDH(high) and ALDH(low) cells. Drug-resistance was evaluated by cell viability, anchorage-independent sphere formation, flow-cytometry and qRT-PCR analyses.
resultsThe ALDH(high) - and ALDH(low) -sorted fractions were able to demonstrate phenotypic heterogeneity and generate spheres, the latter being less efficient, and both showed an association with CD44. Cis- diamminedichloroplatinum (II) (cisplatin) treatment failed to reduce ALDH activity and conferred only a short-term inhibition of sphere generation in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Induction of drug sensitivity by an ALDH inhibitor, diethylaminobenzaldehyde (DEAB) resulted in significant reductions in cell viability but not a complete elimination of the sphere-forming cells, suggestive of the presence of a drug-resistant subpopulation. At the transcript level, the cisplatin + DEAB-resistant cells showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44 indicating the involvement of these markers in conferring chemoresistance in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines.
conclusionsOur study shows that ALDH(high) CD44(+) cells are implicated in conveying tolerance to cisplatin in the three MPM cell lines. The combined use of CD44 and ALDH widens the window for identification and targeting of a drug-resistant population which may improve the current treatment modalities in mesothelioma.
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