Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus

Autor: William H. Baird, Yonatan Y. Mahller, Timothy P. Cripe, Nancy Ratner, Yoshinaga Saeki, Jon P. Williams, Jose A. Cancelas, Jonathan Grossheim, Bryan Mitton
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Transcription
Genetic
Cellular differentiation
medicine.medical_treatment
lcsh:Medicine
Nestin
Neuroblastoma
0302 clinical medicine
Intermediate Filament Proteins
Chlorocebus aethiops
ATP Binding Cassette Transporter
Subfamily G
Member 2
AC133 Antigen
lcsh:Science
0303 health sciences
Multidisciplinary
Stem Cells
Stem-cell therapy
Neural stem cell
3. Good health
Neoplasm Proteins
Gene Expression Regulation
Neoplastic
Oncolytic Viruses
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Stem cell
Research Article
Nerve Tissue Proteins
Biology
03 medical and health sciences
Cancer stem cell
Antigens
CD
Cell Line
Tumor
medicine
Animals
Humans
Cell Lineage
Progenitor cell
Molecular Biology
Vero Cells
030304 developmental biology
Glycoproteins
lcsh:R
medicine.disease
Oncolytic virus
Immunology
Cancer research
lcsh:Q
Oncology/Pediatric Oncology
ATP-Binding Cassette Transporters
Peptides
Virology/Viruses and Cancer
Zdroj: PLoS ONE
PLoS ONE, Vol 4, Iss 1, p e4235 (2009)
ISSN: 1932-6203
Popis: Background 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. Methodology/Principal Findings 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. Conclusions/Significance These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.
Databáze: OpenAIRE
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