title: Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity.
abstract: Tumor cells often express phenotypic markers that are specific to the cells from which they originated. A neural RNA-binding protein, Musashil, is an evolutionarily well-conserved marker for neural stem cells/ progenitor cells. To examine the origin of gliomas, we examined the expression of the human Musashil homolog, MSI1, in human glioma tissues and in normal human adult and fetal brains. As we had seen previously in rodents, in the normal human brain, MSI1 was expressed in cells located in the ventricular and subventricular zones, in GFAP-negative glial cells, and in GFAP-positive astrocytes. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GFAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. The percentage of MSI1-labeled tumor cells increased in higher-grade astrocytomas and correlated with proliferative activity, as estimated by an MIB-1 staining index. Our results indicate that MSI1 is an excellent marker for neural progenitor cells including neural stem cells in normal human brains. Furthermore, the expression of MSI1 correlates well with the immature nature as well as the malignancy of tumor cells in human gliomas. Thus, we expect the analysis of MSI1 expression to contribute to the understanding of the cellular origin and biology of human gliomas.
authors.affiliation: Institute for Clinical Research, Osaka National Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanemura
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Sakakibara
authors.forename: H
authors.initials: H
authors.lastname: Fujikawa
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: A
authors.initials: A
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: S
authors.initials: S
authors.lastname: Fushiki
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: H
authors.initials: H
authors.lastname: Okano
authors.forename: N
authors.initials: N
authors.lastname: Arita
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D016543:Central Nervous System Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019143:Evolution, Molecular; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012016:Reference Values; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: D014408:Biomarkers, Tumor; C491297:MSI1 protein, human; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors