ArticleJournal of experimental & clinical cancer research : CR2015
Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells.International journal of molecular sciences · 2025Review
- New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.Journal of cellular and molecular medicine · 2024Article
- Exposure of Bladder Cancer Cells to Blue Light (λ = 453 nm) in the Presence of Riboflavin Synergistically Enhances the Cytotoxic Efficiency of Gemcitabine.International journal of molecular sciences · 2024Article
- Downregulation of the keratins CK13 and CK14 does not significantly affect cell viability of human urinary bladder carcinoma cells.Contemporary oncology (Poznan, Poland) · 2024Article
- Tumorigenic effects of human mesenchymal stromal cells and fibroblasts on bladder cancer cells.Frontiers in oncology · 2023Article
- Epigenetic Priming and Development of New Combination Therapy Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration.Journal of oncology · 2022Article
- The Role of lncRNAs in the Stem Phenotype of Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2021Review
- Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.Cancers · 2021Article
- Cancer stem cells: a major culprit of intra-tumor heterogeneity.American journal of cancer research · 2021Review
- Chorioallantoic urothelial tumor avatar. A clinical tool for phenotype-based therapy.Acta cirurgica brasileira · 2020Review
- [Matrine suppresses stemness of hepatocellular carcinoma cells by regulating β-catenin signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Distinctive mutational spectrum and karyotype disruption in long-term cisplatin-treated urothelial carcinoma cell lines.Scientific reports · 2019Article
- Treatment resistance in urothelial carcinoma: an evolutionary perspective.Nature reviews. Clinical oncology · 2018Review
- The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.Clinical & experimental metastasis · 2018Review
- Multifaceted Mechanisms of Cisplatin Resistance in Long-Term Treated Urothelial Carcinoma Cell Lines.International journal of molecular sciences · 2018Article
- Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity.Frontiers in oncology · 2018Review
- Various Mechanisms Involve the Nuclear Factor (Erythroid-Derived 2)-Like (NRF2) to Achieve Cytoprotection in Long-Term Cisplatin-Treated Urothelial Carcinoma Cell Lines.International journal of molecular sciences · 2017Article
- The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors.Bladder cancer (Amsterdam, Netherlands) · 2016Article
- Spheres derived from the human SN12C renal cell carcinoma cell line are enriched in tumor initiating cells.Journal of experimental & clinical cancer research : CR · 2016Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro.
methodsMagnetic- and fluorescence-activated- cell sorting were used for separation of CD90(+) and CD90(-) UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs.
resultsWe observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90(+) cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90(+) cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90(+) cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes.
conclusionsOur findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.
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