CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV†
Joseph G. Pressey MD
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorMarilyn C. Haas BA
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorChristine S. Pressey BS
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorVirginia M. Kelly BS
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorJacqueline N. Parker PhD
Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorG. Yancey Gillespie PhD
Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorCorresponding Author
Gregory K. Friedman MD
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Department of Pediatrics, Division of Hematology and Oncology, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 512, Birmingham, AL 35233.===Search for more papers by this authorJoseph G. Pressey MD
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorMarilyn C. Haas BA
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorChristine S. Pressey BS
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorVirginia M. Kelly BS
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorJacqueline N. Parker PhD
Division of Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorG. Yancey Gillespie PhD
Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorCorresponding Author
Gregory K. Friedman MD
Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama
Department of Pediatrics, Division of Hematology and Oncology, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 512, Birmingham, AL 35233.===Search for more papers by this authorConflict of interest: Nothing to declare.
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.
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. Pediatr Blood Cancer 2013; 60: 45–52. © 2012 Wiley Periodicals, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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