Conflict of interest: Nothing to declare.
CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV†
Article first published online: 9 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer
Volume 60, Issue 1, pages 45–52, January 2013
How to Cite
Pressey, J. G., Haas, M. C., Pressey, C. S., Kelly, V. M., Parker, J. N., Gillespie, G. Y. and Friedman, G. K. (2013), CD133 marks a myogenically primitive subpopulation in rhabdomyosarcoma cell lines that are relatively chemoresistant but sensitive to mutant HSV. Pediatr. Blood Cancer, 60: 45–52. doi: 10.1002/pbc.24117
- Issue published online: 15 NOV 2012
- Article first published online: 9 MAR 2012
- Manuscript Accepted: 2 FEB 2012
- Manuscript Received: 19 JAN 2012
- National Cancer Institute/National Institutes of Health (NIH). Grant Number: CA071933
- NIH. Grant Number: P30 #AR48311
- Kaul Pediatric Research Institute
- cancer stem cells;
- herpes simplex virus;
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.
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).
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.
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.