Up-regulation of neuropoiesis generating glial progenitors that infiltrate rat intracranial glioma.
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.
Duntsch
Christopher
C
Department of Neurosurgery, The University of Tennessee Health Science Center, 847 Monroe Avenue, Suite 427, Memphis, TN 38163, USA. duntsch@bellsouth.net
Zhou
Qihong
Q
Weimar
James D
JD
Frankel
Bruce
B
Robertson
Jon H
JH
Pourmotabbed
Tayebeh
T
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin
Brain Res. 1999 Sep 4;840(1-2):153-7
10517963
J Neurooncol. 1999 Mar;42(1):59-67
10360479
J Neurosci. 1988 Apr;8(4):1144-51
3357014
Trends Neurosci. 1997 Dec;20(12):570-7
9416670
Glia. 2002 Sep;39(3):193-206
12203386
Neuron. 1993 Jul;11(1):173-89
8338665
Exp Neurol. 2002 Mar;174(1):89-95
11869037
Science. 1968 Jul 26;161(3839):370-1
4873531
Brain Res. 1999 Aug 14;838(1-2):1-10
10446310
CA Cancer J Clin. 2002 Jan-Feb;52(1):23-47
11814064
Cell. 1999 Jun 11;97(6):703-16
10380923
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12846-51
11070094
Virchows Arch B Cell Pathol. 1978 Jul 14;28(1):77-85
97859
Neuroreport. 1994 Oct 3;5(15):1885-8
7841369
J Neurosci. 1996 Dec 1;16(23):7599-609
8922416
Neurosurgery. 1990 Apr;26(4):622-8
2330084
J Neurosurg. 1981 Apr;54(4):461-7
7205347
Neurosurgery. 2001 Jul;49(1):168-75; discussion 175-6
11440439
Science. 1992 Mar 27;255(5052):1707-10
1553558
J Neurooncol. 2003 Aug-Sep;64(1-2):31-44
12952284
Cancer Res. 1992 Oct 1;52(19):5334-41
1382841
Neuroreport. 1999 Apr 6;10(5):1007-11
10321476
Brain Res. 1997 Sep 12;768(1-2):1-9
9369294
J Neurosci. 1997 Jul 1;17(13):5046-61
9185542
Pediatr Neurosurg. 1992;18(5-6):310-4
1476942
J Cell Biol. 1995 Oct;131(2):453-64
7593171
J Neurosci. 1996 Apr 15;16(8):2649-58
8786441
Curr Opin Neurol. 2001 Dec;14(6):683-8
11723374
Trends Neurosci. 1994 Apr;17(4):138-42
7517589
Mol Cell Neurosci. 1995 Oct;6(5):474-86
8581317
J Neurooncol. 1998 Nov;40(2):151-60
9892097
Am J Pathol. 2001 Sep;159(3):779-86
11549567
J Neurosurg. 2001 Sep;95(3):459-65
11565868
J Neurosci Res. 2000 Aug 15;61(4):421-9
10931528
Neuron. 1994 Nov;13(5):1071-82
7946346
Cell. 1990 Feb 23;60(4):585-95
1689217
Am J Pathol. 1997 Aug;151(2):565-71
9250169
Carcinogenesis. 1998 Sep;19(9):1529-37
9771921
J Neurosurg. 1980 Dec;53(6):808-15
7003068