PMID- 20468047 OWN - NLM STAT- MEDLINE DCOM- 20100826 LR - 20211020 IS - 1098-1136 (Electronic) IS - 0894-1491 (Linking) VI - 58 IP - 9 DP - 2010 Jul TI - Glial progenitors in the brainstem give rise to malignant gliomas by platelet-derived growth factor stimulation. PG - 1050-65 LID - 10.1002/glia.20986 [doi] AB - Glial progenitors in the white matter and the subventricular zone are the major population of cycling cells in the postnatal central nervous system, and thought to be candidates for glioma-initiating cells. However, less is known about the dividing cell populations in the brainstem than those in the cerebrum, leading to the lag of basic understanding of brainstem gliomas. We herein demonstrate much fewer cycling glial progenitors exist in the brainstem than in the cerebrum. We also show that infecting brainstem glial progenitors with PDGFB-green fluorescent protein (GFP)-expressing retrovirus induced tumors that closely resembled human malignant gliomas. Of note, brainstem tumors grew more slowly than cerebral tumors induced by the same retrovirus, and >80% tumor cells in the brainstem consisted of GFP-positive, infected progenitors while GFP-positive cells in the cerebral tumors were <20%. These indicate that cerebral tumors progressed rapidly by recruiting resident progenitors via paracrine mechanism whereas brainstem tumors grew more slowly by clonal expansion of the infected population. The cerebral and brainstem glial progenitors similarly showed reversible dedifferentiation upon PDGF stimulation in vitro and did not show the intrinsic difference in terms of the responsiveness to PDGF. We therefore suggest that slower, monoclonal progression pattern of the brainstem tumors is at least partly due to the environmental factors including the cell density of the glial progenitors. Together, these findings are the first implications regarding the cell-of-origin and the gliomagenesis in the brainstem. CI - Copyright 2010 Wiley-Liss, Inc. FAU - Masui, Kenta AU - Masui K AD - Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Suzuki, Satoshi O AU - Suzuki SO FAU - Torisu, Rina AU - Torisu R FAU - Goldman, James E AU - Goldman JE FAU - Canoll, Peter AU - Canoll P FAU - Iwaki, Toru AU - Iwaki T LA - eng GR - R01 NS066955/NS/NINDS NIH HHS/United States PT - Journal Article PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Platelet-Derived Growth Factor) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Brain Neoplasms/physiopathology MH - Brain Stem/pathology/*physiopathology MH - Brain Stem Neoplasms/pathology/*physiopathology MH - Cell Differentiation MH - Cells, Cultured MH - Cerebellum/physiology MH - Child MH - Female MH - Genes, sis MH - Genetic Vectors MH - Glioma/pathology/*physiopathology MH - Green Fluorescent Proteins/genetics MH - Humans MH - Male MH - Neuroglia/*physiology MH - Platelet-Derived Growth Factor/genetics/*metabolism MH - Rats MH - Retroviridae MH - Stem Cells/*physiology EDAT- 2010/05/15 06:00 MHDA- 2010/08/27 06:00 CRDT- 2010/05/15 06:00 PHST- 2010/05/15 06:00 [entrez] PHST- 2010/05/15 06:00 [pubmed] PHST- 2010/08/27 06:00 [medline] AID - 10.1002/glia.20986 [doi] PST - ppublish SO - Glia. 2010 Jul;58(9):1050-65. doi: 10.1002/glia.20986.