Developmental signaling pathways in brain tumor-derived stem-like cells.
Recently, a subpopulation of cells highly efficient in tumor initiation and growth has been isolated from brain tumors. Of interest, these brain tumor initiating cells exhibit many stem-like properties, including self-renewal, extended proliferation, and multipotency, and are both phenotypically and genetically similar to normal neural stem cells (NSCs). Aberrant expression of developmental pathways, such as WNT, Hedgehog, Notch, and transforming growth factor-beta/bone morphogenetic protein, have been demonstrated in brain tumors, and extrinsic regulation of these pathways may be used to target brain tumor stem-like cells (BTSCs) and form the basis of novel biological therapies. Because of regulatory redundancy during normal development, future therapeutic strategies to inhibit BTSC-mediated tumor growth and minimize NSC-related deleterious effects may require detailed understanding and regulation of multiple cellular mechanisms. This review analyzes the role developmental pathways play in brain tumors, focusing on the potential effects of pathway regulation on BTSC-driven tumorigenesis.
Clark
Paul A
PA
Brain Tumor Research Lab, Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792-8660, USA.
Treisman
Daniel M
DM
Ebben
Johnathan
J
Kuo
John S
JS
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000254:growth & development; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D014411:Neoplastic Stem Cells / Q000145:classification / Q000473:pathology / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins