Prominin-1 (CD133) defines both stem and non-stem cell populations in CNS development and gliomas
| Autor: | Emily Learner, Sam Haidar, Keith L. Ligon, Cecile L. Maire, Monica Nistér, Karl Holmberg Olausson, Jason Ling |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Pathology lcsh:Medicine Central Nervous System Neoplasms Mice Neural Stem Cells Animal Cells Medicine and Health Sciences AC133 Antigen lcsh:Science Neurological Tumors In Situ Hybridization Multidisciplinary Stem Cells Brain Gene Expression Regulation Developmental Glioma Neural stem cell Gene Expression Regulation Neoplastic Neurology Oncology Neoplastic Stem Cells Stem cell Cellular Types Adult stem cell Research Article medicine.medical_specialty Biology OLIG2 SOX2 Developmental Neuroscience Cancer stem cell Antigens CD Prominin-1 medicine Animals Humans Cell Lineage Progenitor cell Glycoproteins lcsh:R Biology and Life Sciences Cancers and Neoplasms Cell Biology Astrocytes Cancer research lcsh:Q Glioblastoma Peptides Neuroscience |
| Zdroj: | PLoS ONE, Vol 9, Iss 9, p e106694 (2014) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|