Glial cell line-derived neurotrophic factor (GDNF) family ligands reduce the sensitivity of neuroblastoma cells to pharmacologically induced cell death, growth arrest and differentiation.
The glial cell line-derived neurotrophic factor (GDNF) family of ligands play essential roles in promoting normal neural crest differentiation during embryogenesis, and, may have a therapeutic role in malignancies of neural crest origin, such as neuroblastoma. However, we report here that GDNF and neurturin blocked the growth inhibitory and neuritogenic effects of all-trans-retinoic acid in neuroblastoma cells in vitro. GDNF caused neuroblastoma cells to proliferate in the presence of a range of cytotoxic chemotherapeutic agents at low concentrations. Thus, our findings suggest a role for GDNF signaling in promoting resistance to differentiation or cytotoxic therapy of neuroblastoma, and, preclude their use in this neural crest tumor.
Hansford
Loen M
LM
Children's Cancer Institute Australia for Medical Research, Sydney, Australia.
Marshall
Glenn M
GM
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000037:antagonists & inhibitors; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051101:Neurturin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000970:Antineoplastic Agents; D003603:Cytotoxins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051098:Glial Cell Line-Derived Neurotrophic Factors; D006131:Growth Inhibitors; D008024:Ligands; D051101:Neurturin; D014212:Tretinoin