title: CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV.
abstract: 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.
  
  
  METHODS
  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.affiliation: Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Pressey
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Haas
authors.forename: Christine S
authors.initials: CS
authors.lastname: Pressey
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Kelly
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Parker
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Friedman
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005818:Genetic Engineering; D006023:Glycoproteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D050130:Oncolytic Virotherapy; D010455:Peptides / Q000032:analysis* / Q000502:physiology; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000032:analysis; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3