Document Detail


CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV.
MedLine Citation:
PMID:  22408058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Rhabdomyosarcoma (RMS) is characterized by features of skeletal muscle and is comprised of two major histological subtypes, embryonal (E-RMS), and alveolar (A-RMS). Subsets of each RMS subtype demonstrate resistance to multimodal therapy leading to treatment failure. Cancer stem cells or cancer-initiating cells (CIC) represent a theorized population of cells that give rise to tumors and are responsible for treatment resistance.
PROCEDURE: We investigated the ability of CD133, a putative CIC marker, to distinguish a chemoresistant, myogenically primitive population in alveolar (RH30), and embryonal (RD) RMS cell lines. We tested CD133+/- cells for sensitivity to engineered herpes simplex virus (oHSV).
RESULTS: Relative to CD133- cells, CD133+ A-RMS, and E-RMS cells demonstrate an enhanced colony-forming ability, are less differentiated myogenically, and are more resistant to cytotoxic chemotherapy but equally sensitive to oHSV oncolysis. Compared to CD133- RD cells, CD133+ cells express relatively high levels of genes typically expressed in skeletal muscle progenitor satellite cells including PAX7, c-MET, and the GLI effectors of the hedgehog signaling pathway. In contrast, CD133+ RH30 cells were not associated with enhanced expression of satellite cell markers or Hh targets.
CONCLUSIONS: Our findings demonstrate that CD133+ cells from A-RMS and E-RMS cell lines are characterized by a myogenically primitive phenotype. These cells have the capacity to form colonies in vitro and are more resistant to chemotherapy than CD133- cells. CD133 expression may denote a subset of RMS cells with an important role in tumorigenesis and treatment failure. These resistant cells may be effectively targeted by oHSV therapy.
Authors:
Joseph G Pressey; Marilyn C Haas; Christine S Pressey; Virginia M Kelly; Jacqueline N Parker; G Yancey Gillespie; Gregory K Friedman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-09
Journal Detail:
Title:  Pediatric blood & cancer     Volume:  60     ISSN:  1545-5017     ISO Abbreviation:  Pediatr Blood Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-03-07     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  101186624     Medline TA:  Pediatr Blood Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  45-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD / analysis*,  physiology
Cell Line, Tumor
Drug Resistance, Neoplasm*
Genetic Engineering
Glycoproteins / analysis*,  physiology
Humans
Oncolytic Virotherapy*
Peptides / analysis*,  physiology
Receptor, Fibroblast Growth Factor, Type 3 / analysis
Rhabdomyosarcoma / chemistry,  drug therapy,  pathology,  therapy*
Signal Transduction
Simplexvirus / genetics*,  physiology*
Grant Support
ID/Acronym/Agency:
CA071933/CA/NCI NIH HHS; P01 CA071933-13/CA/NCI NIH HHS; P30 #AR48311/AR/NIAMS NIH HHS; P30 AR048311/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/Glycoproteins; 0/Peptides; EC 2.7.10.1/FGFR3 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3
Comments/Corrections

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


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