title: Prominin-1 (CD133) defines both stem and non-stem cell populations in CNS development and gliomas.
abstract: Prominin-1 (CD133) is a commonly used cancer stem cell marker in central nervous system (CNS) tumors including glioblastoma (GBM). Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi)). Lineage marker analysis reveals Prom1(hi) cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi) cells. Bromodeoxyuridine labeling identifies Prom1(hi) as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX) - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H) mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Department of Oncology Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Holmberg Olausson
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Cecile L
authors.initials: CL
authors.lastname: Maire
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Sam
authors.initials: S
authors.lastname: Haidar
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Ling
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Learner
authors.affiliation: Department of Oncology Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Monica
authors.initials: M
authors.lastname: Nistér
authors.affiliation: Center for Molecular Oncologic Pathology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism*; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse