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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas
Devraj Basu1, Kathleen T Montone, Li-Ping Wang
1Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA. devraj.basu@uphs.upenn.edu
Cell Cycle (Georgetown, Tex.)
|May 12, 2011
Summary
Mesenchymal-like squamous cell carcinoma (SCC) cells resist chemotherapy. Salinomycin effectively targets these drug-resistant SCC cells, unlike cisplatin, offering a potential new treatment strategy for advanced SCC.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Chemotherapy often fails to eradicate all cancer cells due to drug-resistant tumor subpopulations.
- Squamous cell carcinoma (SCC) exhibits mesenchymal-like cells (Ecad-lo) with phenotypic plasticity and resistance to current agents.
- These Ecad-lo cells are distinct from epithelial-like (Ecad-hi) cells, identified by E-cadherin loss and vimentin expression.
Purpose of the Study:
- To investigate the differential sensitivity of Ecad-lo and Ecad-hi SCC cells to cisplatin and salinomycin.
- To determine the in vivo relevance of mesenchymal-like cells in advanced SCC and their response to treatment.
Main Methods:
- Purification and in vitro culture of Ecad-lo and Ecad-hi SCC cell lines.
- Treatment of purified cell populations with cisplatin and salinomycin.
- Immunohistochemical analysis of vimentin-positive cells in patient-derived xenografts (DTXs) of advanced SCC.
- Assessment of drug efficacy in vivo using DTX models.
Main Results:
- Cisplatin selectively depleted Ecad-hi cells, sparing Ecad-lo cells.
- Salinomycin demonstrated comparable efficacy against both Ecad-hi and Ecad-lo cells.
- In vivo, cisplatin treatment enriched vimentin-positive (mesenchymal-like) cells in residual tumors, while salinomycin depleted this subpopulation.
Conclusions:
- Mesenchymal-like SCC cells, resistant to conventional chemotherapy, are sensitive to salinomycin.
- Salinomycin represents a promising therapeutic strategy for targeting drug-resistant SCC subpopulations.
- Mesenchymal-like SCC cells are prevalent in advanced stages, highlighting the clinical relevance of targeting this subpopulation.
