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Up-regulation of neuropoiesis generating glial progenitors that infiltrate ratintracranial glioma

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Abstract

To investigate adult neural stem cell (NSC) biology in relation to glioma, the C6 glioma cell line was tagged with green fluorescent protein (GFP) and inoculated into the brain of adult rats. The in vivo biological response of the brain to glioma was studied using immunohistochemical analysis of the subventricular zone (SVZ), peritumoral areas, and glioma. Nestin immunoreactive cells were found infiltrating glioma, but the distribution of abnormal immunoreactivity was restricted to the dorsal and medial border of the tumor relative to the ipsilateral ventricle. The SVZ was found to be hypertrophic, hypercellular, and up-regulated nestin expression. Furthermore, a dense contiguous population of nestin immunoreactive cells could be found streaming from ipsilateral dorsal tip of the SVZ, tracking along the ventral margin of the corpus callosum, and fanning out to encompass and infiltrate the proximal tumor border. Although most cells were either nestin or glial fibrillary acidic protein (GFAP) immunoreactive in the SVZ and along the ventral margin of the corpus callosum, the number of cells co-expressing both markers increased proportionally as the tumor was approached so that the predominant cell population along the proximal tumor border was GFAP immunoreactive. Finally, we demonstrated that a significant proportion of cells found in areas of abnormal immunoreactivity were proliferating, especially in peritumoral areas. In summary, there is an induction of neuropoietic activity in a rat intracranial glioma model that results in an infiltration and accumulation of abnormal nestin and GFAP expressing cells with proliferative potential along the dorsal and medial border of intracranial C6 glioma.

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References

  • A Jemal A Thomas T Murray M Thun (2002) ArticleTitleCancer statistics, 2002 CA Cancer J Clin 52 23–47 Occurrence Handle11814064

    PubMed  Google Scholar 

  • TS Surawicz F Davis S Freels ER Laws SuffixJr HR Menck (1998) ArticleTitleBrain tumor survival: results from the National Cancer Data Base J Neurooncol 40 151–160 Occurrence Handle10.1023/A:1006091608586 Occurrence Handle1:STN:280:DyaK1M7gslWitw%3D%3D Occurrence Handle9892097

    Article  CAS  PubMed  Google Scholar 

  • DN Louis EC Holland JG Cairncross (2001) ArticleTitleGlioma classification: a molecular reappraisal Am J Pathol 159 779–786

    Google Scholar 

  • EC Holland (2001) ArticleTitleProgenitor cells and glioma formation Curr Opin Neurol 14 683–688

    Google Scholar 

  • TN Ignatova VG Kukekov ED Laywell ON Suslov FD Vrionis DA Steindler (2002) ArticleTitleHuman cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro Glia 39 193–206

    Google Scholar 

  • U Lendahl LB Zimmerman RD McKay (1990) ArticleTitleCNS stem cells express a new class of intermediate filament protein Cell 60 585–595 Occurrence Handle1:CAS:528:DyaK3cXkvFagsro%3D Occurrence Handle1689217

    CAS  PubMed  Google Scholar 

  • CM Morshead BA Reynolds CG Craig MW McBurney WA Staines D Morassutti S Weiss D Kooy Particlevan der (1994) ArticleTitleNeural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells Neuron 13 1071–1082

    Google Scholar 

  • BA Reynolds S Weiss (1992) ArticleTitleGeneration of neurons and astrocytes from isolated cells of the adult mammalian central nervous system Science 255 1707–1710 Occurrence Handle1:STN:280:By2B3crjsFU%3D Occurrence Handle1553558

    CAS  PubMed  Google Scholar 

  • J Dahlstrand VP Collins U Lendahl (1992) ArticleTitleExpression of the class VI intermediate filament nestin in human central nervous system tumors Cancer Res 52 5334–5341

    Google Scholar 

  • K Frederiksen RD McKay (1988) ArticleTitleProliferation and differentiation of rat neuroepithelial precursor cells in vivo J Neurosci 8 1144–1151

    Google Scholar 

  • KS Aboody A Brown NG Rainov KA Bower S Liu W Yang JE Small U Herrlinger V Ourednik PM Black XO Breakefield EY Snyder (2000) ArticleTitleNeural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas Proc Natl Acad Sci USA 97 12846–12851 Occurrence Handle10.1073/pnas.97.23.12846 Occurrence Handle1:CAS:528:DC%2BD3cXotFyksrc%3D Occurrence Handle11070094

    Article  CAS  PubMed  Google Scholar 

  • CG Craig V Tropepe CM Morshead BA Reynolds S Weiss D Kooy Particlevan der (1996) ArticleTitleIn vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain J Neurosci 16 2649–2658

    Google Scholar 

  • F Doetsch I Caille DA Lim JM Garcia-Verdugo A Alvarez-Buylla (1999) ArticleTitleSubventricular zone astrocytes are neural stem cells in the adult mammalian brain Cell 97 703–716 Occurrence Handle10.1016/S0092-8674(00)80783-7 Occurrence Handle1:CAS:528:DyaK1MXjvFOju78%3D Occurrence Handle10380923

    Article  CAS  PubMed  Google Scholar 

  • F Doetsch JM Garcia-Verdugo A Alvarez-Buylla (1997) ArticleTitleCellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain J Neurosci 17 5046–5061

    Google Scholar 

  • MB Luskin (1993) ArticleTitleRestricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone Neuron 11 173–189

    Google Scholar 

  • TD Palmer J Ray FH Gage (1995) ArticleTitleFGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain Mol Cell Neurosci 6 474–486 Occurrence Handle10.1006/mcne.1995.1035 Occurrence Handle1:CAS:528:DyaK2MXpsVGks78%3D Occurrence Handle8581317

    Article  CAS  PubMed  Google Scholar 

  • S Weiss C Dunne J Hewson C Wohl M Wheatley AC Peterson BA Reynolds (1996) ArticleTitleMultipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis J Neurosci 16 7599–7609

    Google Scholar 

  • SC Barnett L Robertson D Graham D Allan R Rampling (1998) ArticleTitleOligodendrocyte-type-2 astrocyte (O-2A) progenitor cells transformed with c-myc and H-ras form high-grade glioma after stereotactic injection into the rat brain Carcinogenesis 19 1529–1537

    Google Scholar 

  • JJ Zhu SP Leon RD Folkerth SZ Guo JK Wu PM Black (1997) ArticleTitleEvidence for clonal origin of neoplastic neuronal and glial cells in gangliogliomas Am J Pathol 151 565–571

    Google Scholar 

  • N Duggal RR Hammond (2002) ArticleTitleNestin expression in ganglioglioma Exp Neurol 174 89–95

    Google Scholar 

  • JP Mickle (1992) ArticleTitleGanglioglioma in children A review of 32 cases at the University of Florida. Pediatr Neurosurg 18 310–314

    Google Scholar 

  • N Duggal S Iskander RR Hammond (2001) ArticleTitleNestin expression in cortical dysplasia J Neurosurg 95 459–465

    Google Scholar 

  • P Benda J Lightbody G Sato L Levine W Sweet (1968) ArticleTitleDifferentiated rat glial cell strain in tissue culture Science 161 370–371 Occurrence Handle1:STN:280:CCeA383lvFM%3D Occurrence Handle4873531

    CAS  PubMed  Google Scholar 

  • JJ Bernstein WJ Goldberg ER Laws SuffixJr D Conger V Morreale LR Wood (1990) ArticleTitleC6 glioma cell invasion and migration of rat brain after neural homografting: ultrastructure Neurosurgery 26 622–628

    Google Scholar 

  • B Frankel SL Longo M Kyle GW Canute TC Ryken (2001) Tumor Fas (APO-1/CD95) up-regulation results in increased apoptosis and survival times for rats with intracranial malignant gliomas. Neurosurgery 49: 168–175 Discussion 166–175

    Google Scholar 

  • N Kobayashi N Allen NR Clendenon LW Ko (1980) ArticleTitleAn improved rat brain-tumor model J Neurosurg 53 808–815

    Google Scholar 

  • M Saini M Bellinzona F Meyer G Cali M Samii (1999) ArticleTitleMorphometrical characterization of two glioma models in the brain of immunocompetent and immunodeficient rats J Neurooncol 42 59–67

    Google Scholar 

  • Sampson JH, E. AG, D. BD: Use of experimental models in neuro-oncological research. In: A C, R H, T HJ (eds) Neurosurgery: The Scientific Basis of Clinical Practice. Blackwell Science, Oxford, 1999, p 596.

  • AM Spence PW Coates (1978) ArticleTitleScanning electron microscopy of cloned astrocytic lines derived from ethylnitrosourea-induced rat gliomas Virchows Arch B Cell Pathol 28 77–85

    Google Scholar 

  • AM Spence JP Geraci (1981) ArticleTitleCombined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model J Neurosurg 54 461–467

    Google Scholar 

  • T Dutta A Spence LA Lampson (2003) ArticleTitleRobust ability of IFN-gamma to upregulate class II MHC antigen expression in tumor bearing rat brains J Neurooncol 64 31–44

    Google Scholar 

  • HK Kimelberg D. NM (1994) Astrocytic responses to central nervous system trauma I FA K SS (Eds) The Neurobiology of Central Nervous System Trauma Oxford UP New York 193–208

    Google Scholar 

  • GA Brook A Perez-Bouza J Noth W Nacimiento (1999) ArticleTitleAstrocytes re-express nestin in deafferented target territories of the adult rat hippocampus Neuroreport 10 1007–1011

    Google Scholar 

  • SR Clarke AK Shetty JL Bradley DA Turner (1994) ArticleTitleReactive astrocytes express the embryonic intermediate neurofilament nestin Neuroreport 5 1885–1888

    Google Scholar 

  • N Duggal R Schmidt-Kastner AM Hakim (1997) ArticleTitleNestin expression in reactive astrocytes following focal cerebral ischemia in rats Brain Res 768 1–9 Occurrence Handle1:CAS:528:DyaK2sXlslelsLc%3D Occurrence Handle9369294

    CAS  PubMed  Google Scholar 

  • J Frisen CB Johansson C Torok M Risling U Lendahl (1995) ArticleTitleRapid, widespread, and longlasting induction of nestin contributes to the generation of glial scar tissue after CNS injury J Cell Biol 131 453–464 Occurrence Handle1:CAS:528:DyaK2MXosFygtb4%3D Occurrence Handle7593171

    CAS  PubMed  Google Scholar 

  • S Sahin Kaya A Mahmood Y Li E Yavuz M Chopp (1999) ArticleTitleExpression of nestin after traumatic brain injury in rat brain Brain Res 840 153–157

    Google Scholar 

  • MK McMillian L Thai JS Hong JP O’Callaghan KR Pennypacker (1994) ArticleTitleBrain injury in a dish: a model for reactive gliosis Trends Neurosci 17 138–142

    Google Scholar 

  • JL Ridet SK Malhotra A Privat FH Gage (1997) ArticleTitleReactive astrocytes: cellular and molecular cues to biological function Trends Neurosci 20 570–577 Occurrence Handle10.1016/S0166-2236(97)01139-9 Occurrence Handle1:CAS:528:DyaK2sXnvFWnt7c%3D Occurrence Handle9416670

    Article  CAS  PubMed  Google Scholar 

  • Y. Li M Chopp (1999) ArticleTitleTemporal profile of nestin expression after focal cerebral ischemia in adult rat Brain Res 838 1–10 Occurrence Handle10.1016/S0006-8993(99)01502-4 Occurrence Handle1:CAS:528:DyaK1MXlt1Shtr8%3D Occurrence Handle10446310

    Article  CAS  PubMed  Google Scholar 

  • Z Kornyei A Czirok T Vicsek E Madarasz (2000) ArticleTitleProliferative and migratory responses of astrocytes to in vitro injury J Neurosci Res 61 421–429

    Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Neurosurgery, The University of Tennessee Health Science Center, 847 Monroe Avenue, Suite 427, 38163, Memphis, TN, USA

    Christopher Duntsch, Qihong Zhou, James D. Weimar, Bruce Frankel, Jon H. Robertson & Tayebeh Pourmotabbed

  2. Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA

    Christopher Duntsch

  3. Department of Neurosurgery, The University of Tennessee Health Science Center, Memphis, TN, USA

    Tayebeh Pourmotabbed

Authors
  1. Christopher Duntsch
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  2. Qihong Zhou
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  3. James D. Weimar
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  4. Bruce Frankel
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  5. Jon H. Robertson
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  6. Tayebeh Pourmotabbed
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Correspondence to Christopher Duntsch.

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Duntsch, C., Zhou, Q., Weimar, J.D. et al. Up-regulation of neuropoiesis generating glial progenitors that infiltrate ratintracranial glioma. J Neurooncol 71, 245–255 (2005). https://doi.org/10.1007/s11060-004-2156-6

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