Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / antagonists & inhibitors*
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Cell Cycle / drug effects
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Cell Cycle / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cytotoxins / antagonists & inhibitors
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Drug Resistance, Neoplasm / drug effects*
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Drug Resistance, Neoplasm / physiology
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Glial Cell Line-Derived Neurotrophic Factor / pharmacology
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Glial Cell Line-Derived Neurotrophic Factors / pharmacology*
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Growth Inhibitors / antagonists & inhibitors
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Growth Inhibitors / pharmacology
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Humans
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Ligands
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Mice
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Mice, Transgenic
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Neuroblastoma / drug therapy*
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Neuroblastoma / metabolism
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Neuroblastoma / physiopathology
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Neurturin / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Tretinoin / antagonists & inhibitors
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Tretinoin / pharmacology
Substances
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Antineoplastic Agents
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Cytotoxins
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factors
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Growth Inhibitors
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Ligands
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Neurturin
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Tretinoin