title: BMP signaling induces astrocytic differentiation of clinically derived oligodendroglioma propagating cells.
abstract: Oligodendrogliomas are a type of glioma that lack detailed investigation because of an inability to cultivate oligodendroglioma cells that faithfully recapitulate their salient qualities. We have successfully isolated and propagated glioma stem-like cells from multiple clinical oligodendroglioma specimens. These oligodendroglioma-propagating cells (OligPC) are multipotent and form xenografts with oligodendroglioma features. Bone morphogenetic proteins (BMP) are considered potent inhibitors of oligodendrogliogenesis during development; therefore, the effects of BMP signaling in OligPCs were characterized. BMP pathway components are expressed by OligPCs and canonical signaling via Smad proteins is intact. This signaling potently depletes CD133-positive OligPCs, decreasing proliferation, and inducing astrocytic differentiation. Furthermore, analyses revealed that cytoplasmic sequestration of the oligodendrocyte differentiation factors OLIG1/2 by the BMP signaling effectors ID2 and ID4 is a plausible underlying mechanism. These findings elucidate the molecular pathways that underlie the effects of BMP signaling on oligodendroglioma stem-like cells.
  
  
  CONCLUSIONS
  Stem-like cells are capable of propagating oligodendrogliomas, and BMP signaling potently diminishes their stemness by inducing astrocytic differentiation, suggesting that BMP activation may be effective as a cancer stem cell-targeted therapy.
authors.affiliation: 303 E. Chicago Avenue, Ward 10-233, Chicago, IL 60611. maya@fsm.northwestern.edu.
authors.forename: Maya
authors.initials: M
authors.lastname: Srikanth
authors.forename: Juno
authors.initials: J
authors.lastname: Kim
authors.forename: Sunit
authors.initials: S
authors.lastname: Das
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental; D014411:Neoplastic Stem Cells / Q000166:cytology*; D009837:Oligodendroglioma / Q000378:metabolism* / Q000503:physiopathology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D019485:Bone Morphogenetic Proteins; D051785:Smad Proteins