Medulloblastoma stem cells.
Medulloblastoma and other embronal brain tumors are similar in appearance and differentiation potential to neural stem and progenitor cells. Expression studies performed using human tumor samples, as well as the analysis of murine transgenic models, suggest that both multipotent cerebellar stem cells and lineage-restricted progenitors of the external germinal layer can be transformed into medulloblastoma by genetic alterations. These molecular changes frequently involve constitutive activation of signaling pathways such as Wnt, Hedgehog, and Notch, which play a key role in non-neoplastic neural stem cells. Pharmacologic blockade of the Hedgehog and Notch pathways suppresses the growth of medulloblastoma in culture and in vivo and may prove effective in targeting the small cancer stem-cell subpopulation required for tumor initiation and long-term propagation.
Fan
Xing
X
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. xingf@med.umichu.edu
Eberhart
Charles G
CG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054278:Embryonal Carcinoma Stem Cells; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins