Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand.
Current therapies for gliomas fail to address their highly infiltrative nature. Standard treatments often leave behind microscopic neoplastic reservoirs, resulting in eventual tumor recurrence. Neural stem cells (NSCs) are capable of tracking disseminating glioma cells. To exploit this tropism to develop a therapeutic strategy that targeted tumor satellites, we inoculated human glioblastoma xenografts with tumor necrosis factor-related apoptosis-inducing ligand-secreting NSCs. This resulted in the dramatic induction of apoptosis in treated tumors and tumor satellites and was associated with significant inhibition of tumor growth. These results add credence to the potential of NSCs as therapeutically effective delivery vehicles for the treatment of intracranial glioma.
Ehtesham
Moneeb
M
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Kabos
Peter
P
Gutierrez
Mervin A R
MA
Chung
Nancy H C
NH
Griffith
Thomas S
TS
Black
Keith L
KL
Yu
John S
JS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000637:transplantation; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D001616:beta-Galactosidase