Document Detail


Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.
MedLine Citation:
PMID:  20838207     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer stem cells (CSCs) are considered to be of particular concern in cancer as they possess inherent properties of self-renewal and differentiation, along with expressing certain genes related to a mesenchymal phenotype. These features favour the promotion of tumour recurrence and metastasis in cancer patients. Thus, the optimal chemotherapeutic treatment should target the CSC population, either by killing these cells and/or by inducing their transition to a more differentiated epithelial-like phenotype. Experiments were carried out on the trastuzumab-resistant human epidermal growth factor receptor 2-overexpressing breast cancer cell line JIMT-1 to unravel the chemotherapeutic effects of the polyamine analogue [1N,12N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44+CD24- CSC population. Furthermore, effects on the properties of self-renewal and epithelial/mesenchymal markers were also investigated. Treatment with PG11047 reduced the CD44+CD24- subpopulation of JIMT-1 cells by approximately 50%, inhibited and/or reduced self-renewal capability of the CSC population, decreased cell motility and induced expression of mesenchymal to epithelial transition-associated proteins that are involved in promoting an epithelial phenotype. By contrast, DFMO slightly increased the CD44+CD24- subpopulation, increased cell motility and the level of mesenchymal-related proteins. DFMO treatment reduced the self-renewal capability of the CSC population. Both PG11047 and DFMO reduced the expression of the human epidermal growth factor receptor 2 protein, which is correlated to malignancy and resistance to trastuzumab in JIMT-1 cells. Our findings indicate that treatment with PG11047 targeted the CSC population by interfering with several stem cell-related properties, such as self-renewal, differentiation, motility and the mesenchymal phenotype.
Authors:
Helena Cirenajwis; Sandra Smiljanic; Gabriella Honeth; Cecilia Hegardt; Laurence J Marton; Stina M Oredsson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-06     Completed Date:  2011-02-04     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  897-906     Citation Subset:  IM    
Affiliation:
Department of Biology, Division of Cell and Organism, Lund University, Lund, Sweden. helena.cirenajwis@cob.lu.se
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal, Humanized
Antigens, CD24 / immunology
Antigens, CD44 / immunology
Antineoplastic Agents / pharmacology
Breast Neoplasms / drug therapy,  pathology
Cell Differentiation / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Drug Resistance, Neoplasm
Eflornithine / pharmacology
Epithelial-Mesenchymal Transition / drug effects
Female
Humans
Neoplasm Metastasis
Neoplasm Recurrence, Local / drug therapy
Neoplastic Stem Cells / drug effects*,  immunology,  pathology
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  physiology
Spermine / analogs & derivatives*,  pharmacology,  physiology*
Chemical
Reg. No./Substance:
0/(N(1),N(12))bis(ethyl)-6,7-dehydrospermine; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antigens, CD24; 0/Antigens, CD44; 0/Antineoplastic Agents; 70052-12-9/Eflornithine; 71-44-3/Spermine; EC 2.7.10.1/Receptor, Epidermal Growth Factor; P188ANX8CK/trastuzumab

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


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