Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus
Open Access
- 21 January 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (1), e4235
- https://doi.org/10.1371/journal.pone.0004235
Abstract
Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers. Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice. These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.Keywords
This publication has 63 references indexed in Scilit:
- Nf1 Mutation Expands an EGFR-Dependent Peripheral Nerve Progenitor that Confers Neurofibroma Tumorigenic PotentialCell Stem Cell, 2008
- Hematopoietic Stem Cell Function and Survival Depend on c-Myc and N-Myc ActivityCell Stem Cell, 2008
- c-Myc Is Required for Maintenance of Glioma Cancer Stem CellsPLOS ONE, 2008
- Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against NeuroblastomaClinical Cancer Research, 2007
- Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cellsBiochemical and Biophysical Research Communications, 2006
- Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biologyNature Methods, 2006
- A Tumorigenic Subpopulation with Stem Cell Properties in MelanomasCancer Research, 2005
- Oncolytic herpes simplex virus mutants are more efficacious than wild‐type adenovirus Type 5 for the treatment of high‐risk neuroblastomas in preclinical modelsPediatric Blood & Cancer, 2004
- Prospective identification of tumorigenic breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2003
- Treatment of High-Risk Neuroblastoma with Intensive Chemotherapy, Radiotherapy, Autologous Bone Marrow Transplantation, and 13-cis-Retinoic AcidThe New England Journal of Medicine, 1999