Document Detail


Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas.
MedLine Citation:
PMID:  21558812     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Curative eradication of all cells within carcinomas is seldom achievable with chemotherapy alone. This limitation may be partially attributable to tumor cell subpopulations with intrinsic resistance to current drugs. Within squamous cell carcinoma (SCC) cell lines, we previously characterized a subpopulation of mesenchymal-like cells displaying phenotypic plasticity and increased resistance to both cytotoxic and targeted agents. These mesenchymal-like (Ecad-lo) cells are separable from epithelial-like (Ecad-hi) cells based on loss of surface E-cadherin and expression of vimentin. Despite their long-term plasticity, both Ecad-lo and Ecad-hi subsets in short-term culture maintained nearly uniform phenotypes after purification. This stability allowed testing of segregated subpopulations for relative sensitivity to the cytotoxic agent cisplatin in comparison to salinomycin, a compound with reported activity against CD44(+)CD24(-) stem-like cells in breast carcinomas. Salinomycin showed comparable efficacy against both Ecad-hi and Ecad-lo cells in contrast to cisplatin, which selectively depleted Ecad-hi cells. An in vivo correlate of these mesenchymal-like Ecad-lo cells was identified by immunohistochemical detection of vimentin-positive malignant subsets across a part of direct tumor xenografts (DTXs) of advanced stage SCC patient samples. Cisplatin treatment of mice with established DTXs caused enrichment of vimentin-positive malignant cells in residual tumors, but salinomycin depleted the same subpopulation. These results demonstrate that mesenchymal-like SCC cells, which resist current chemotherapies, respond to a treatment strategy developed against a stem-like subset in breast carcinoma. Further, they provide evidence of mesenchymal-like subsets being well-represented across advanced stage SCCs, suggesting that intrinsic drug resistance in this subpopulation has high clinical relevance.
Authors:
Devraj Basu; Kathleen T Montone; Li-Ping Wang; Phyllis A Gimotty; Rachel Hammond; J Alan Diehl; Anil K Rustgi; John T Lee; Kati Rasanen; Gregory S Weinstein; Meenhard Herlyn
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-15
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  10     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-30     Completed Date:  2011-11-02     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2008-16     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / drug therapy
Carcinoma, Squamous Cell / drug therapy,  pathology*
Cell Culture Techniques
Cell Line, Tumor
Cisplatin / pharmacology
Drug Resistance, Neoplasm / drug effects*
Humans
Mesenchymal Stromal Cells / drug effects,  pathology*
Mice
Pyrans / pharmacology
Transplantation, Heterologous
Grant Support
ID/Acronym/Agency:
P01 CA098101/CA/NCI NIH HHS; P01 CA098101/CA/NCI NIH HHS; P30 CA010815/CA/NCI NIH HHS; P30 CA016520/CA/NCI NIH HHS; P30 CA10815/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Pyrans; 62UXS86T64/salinomycin; Q20Q21Q62J/Cisplatin
Comments/Corrections
Comment In:
Cell Cycle. 2011 Aug 15;10(16):2626-7   [PMID:  21836394 ]
Cell Cycle. 2011 Sep 1;10(17):2834-5   [PMID:  21964299 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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