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Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.

Cirenajwis, Helena LU ; Smiljanic, Sandra; Honeth, Gabriella LU ; Hegardt, Cecilia LU ; Marton, Laurence J and Oredsson, Stina LU (2010) In Anti-Cancer Drugs 21(10). p.897-906
Abstract
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... (More)
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 [N,N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44CD24 CSC population. Furthermore, effects on the properties of self-renewal and epithelial/mesenchymal markers were also investigated. Treatment with PG11047 reduced the CD44CD24 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 CD44CD24 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mesenchymal-to-epithelial transition, breast cancer stem cells, [N-1, N-12]bis(ethyl)-cis-6, 7-dehydrospermine, polyamine analogue
in
Anti-Cancer Drugs
volume
21
issue
10
pages
897 - 906
publisher
Rapid Communications
external identifiers
  • wos:000282599900003
  • scopus:78650045248
ISSN
0959-4973
DOI
10.1097/CAD.0b013e32833f2f77
language
English
LU publication?
yes
id
daa1399f-3805-4a3f-b867-a4028763c866 (old id 1688274)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20838207?dopt=Abstract
date added to LUP
2010-10-05 09:54:33
date last changed
2018-07-01 03:22:45
@article{daa1399f-3805-4a3f-b867-a4028763c866,
  abstract     = {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 [N,N]bis(ethyl)-cis-6,7-dehydrospermine (PG11047) and of the polyamine biosynthetic inhibitor 2-difluoromethylornithine (DFMO) on the CD44CD24 CSC population. Furthermore, effects on the properties of self-renewal and epithelial/mesenchymal markers were also investigated. Treatment with PG11047 reduced the CD44CD24 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 CD44CD24 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.},
  author       = {Cirenajwis, Helena and Smiljanic, Sandra and Honeth, Gabriella and Hegardt, Cecilia and Marton, Laurence J and Oredsson, Stina},
  issn         = {0959-4973},
  keyword      = {mesenchymal-to-epithelial transition,breast cancer stem cells,[N-1,N-12]bis(ethyl)-cis-6,7-dehydrospermine,polyamine analogue},
  language     = {eng},
  number       = {10},
  pages        = {897--906},
  publisher    = {Rapid Communications},
  series       = {Anti-Cancer Drugs},
  title        = {Reduction of the putative CD44+CD24- breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047.},
  url          = {http://dx.doi.org/10.1097/CAD.0b013e32833f2f77},
  volume       = {21},
  year         = {2010},
}