Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs r...

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Main Authors: Li Shengwen, Vu Long T, Ho Hector W, Yin Hong, Keschrumrus Vic, Lu Qiang, Wang Jun, Zhang Heying, Ma Zhiwei, Stover Alexander, Weiss John H, Schwartz Philip H, Loudon William G
Format: Article
Language:English
Published: BMC 2012-09-01
Series:Cancer Cell International
Subjects:
Online Access:http://www.cancerci.com/content/12/1/41
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author Li Shengwen
Vu Long T
Ho Hector W
Yin Hong
Keschrumrus Vic
Lu Qiang
Wang Jun
Zhang Heying
Ma Zhiwei
Stover Alexander
Weiss John H
Schwartz Philip H
Loudon William G
author_facet Li Shengwen
Vu Long T
Ho Hector W
Yin Hong
Keschrumrus Vic
Lu Qiang
Wang Jun
Zhang Heying
Ma Zhiwei
Stover Alexander
Weiss John H
Schwartz Philip H
Loudon William G
author_sort Li Shengwen
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall.</p> <p>Methods</p> <p>We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques.</p> <p>Results</p> <p>The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice.</p> <p>Conclusions</p> <p>This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are likely the driving force for the rapid recurrence of the tumor in the patient.</p>
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spelling doaj.art-40cae55c2b9544188992333306d8d1272022-12-22T00:26:48ZengBMCCancer Cell International1475-28672012-09-011214110.1186/1475-2867-12-41Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wallLi ShengwenVu Long THo Hector WYin HongKeschrumrus VicLu QiangWang JunZhang HeyingMa ZhiweiStover AlexanderWeiss John HSchwartz Philip HLoudon William G<p>Abstract</p> <p>Background</p> <p>The cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall.</p> <p>Methods</p> <p>We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques.</p> <p>Results</p> <p>The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice.</p> <p>Conclusions</p> <p>This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are likely the driving force for the rapid recurrence of the tumor in the patient.</p>http://www.cancerci.com/content/12/1/41Glioblastoma multiformePrimary tumorsBrain tumor stem cellsCancer stem cellsOrganotypic brain slice culture
spellingShingle Li Shengwen
Vu Long T
Ho Hector W
Yin Hong
Keschrumrus Vic
Lu Qiang
Wang Jun
Zhang Heying
Ma Zhiwei
Stover Alexander
Weiss John H
Schwartz Philip H
Loudon William G
Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
Cancer Cell International
Glioblastoma multiforme
Primary tumors
Brain tumor stem cells
Cancer stem cells
Organotypic brain slice culture
title Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
title_full Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
title_fullStr Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
title_full_unstemmed Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
title_short Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
title_sort cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall
topic Glioblastoma multiforme
Primary tumors
Brain tumor stem cells
Cancer stem cells
Organotypic brain slice culture
url http://www.cancerci.com/content/12/1/41
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