Expression of integrin αvβ3 in gliomas correlates with tumor grade and is not restricted to tumor vasculature

被引：149
作者：
Schnell, Oliver [2 ]
Krebs, Bjarne [1 ]
Wagner, Erika [2 ]
Romagna, Alexander [2 ]
Beer, Ambros J. [3 ]
Grau, Stefan J. [2 ]
Thon, Niklas [2 ]
Goetz, Claudia [2 ]
Kretzschmar, Hans A. [1 ]
Tonn, Joerg-Christian [2 ]
Goldbrunner, Roland H. [2 ]
机构：
[1] Univ Munich, Ctr Neuropathol & Prion Res, D-81377 Munich, Germany
[2] Univ Munich, Dept Neurosurg, D-81377 Munich, Germany
[3] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-8000 Munich, Germany
来源：
BRAIN PATHOLOGY | 2008年 / 18卷 / 03期
关键词：
angiogenesis; glioma; integrin alpha(v)beta(3); integrin immunohistochemistry; tumor vasculature;
D O I：
10.1111/j.1750-3639.2008.00137.x
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of alpha(v)beta(3) integrin caused by malignancy. The aim of our study was to assess the extent and pattern of alpha(v)beta(3) integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of alpha(v)beta(3) integrin and quantified by an imaging software. The expression of alpha(v)beta(3) was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of alpha(v)beta(3) integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the beta(3) integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of alpha(v)beta(3) integrin in gliomas and are of relevance for the inhibition of alpha(v)beta(3) integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth.
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页码：378 / 386
页数：9
相关论文
共 41 条
[1]  
[Anonymous], 2000, World Health Organisation Classification of Tumours: Pathology and genetics of tumours of the nervous system
[2]   Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all αv integrins [J].
Bader, BL ;
Rayburn, H ;
Crowley, D ;
Hynes, RO .
CELL, 1998, 95 (04) :507-519
[3]   Molecular imaging with new PET tracers [J].
Beer A.J. ;
Schwaiger M. .
Der Radiologe, 2007, 47 (1) :8-17
[4]  
Beer AJ, 2005, J NUCL MED, V46, P1333
[5]   Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin αvβ3 expression in man [J].
Beer, Ambros J. ;
Haubner, Roland ;
Sarbia, Mario ;
Goebel, Michael ;
Luderschmidt, Stephan ;
Grosu, Anca Ligia ;
Schnell, Oliver ;
Niemeyer, Markus ;
Kessler, Horst ;
Wester, Hans-Juergen ;
Weber, Wolfgang A. ;
Schwaiger, Markus .
CLINICAL CANCER RESEARCH, 2006, 12 (13) :3942-3949
[6]   IS201, a specific αvβ3 integrin inhibitor, reduces glioma growth in vivo [J].
Bello, L ;
Lucini, V ;
Giussani, C ;
Carrabba, G ;
Pluderi, M ;
Scaglione, F ;
Tornei, G ;
Villani, R ;
Black, PM ;
Bikfalvi, A ;
Carroll, RS .
NEUROSURGERY, 2003, 52 (01) :177-185
[7]  
Bello L, 2001, CANCER RES, V61, P8730
[8]   αvβ3 and αvβ5 integrin expression in glioma periphery [J].
Bello, L ;
Francolini, M ;
Marthyn, P ;
Zhang, JP ;
Carroll, RS ;
Nikas, DC ;
Strasser, JF ;
Villani, R ;
Cheresh, DA ;
Black, PM .
NEUROSURGERY, 2001, 49 (02) :380-389
[9]   Identification of a novel class of small-molecule antiangiogenic agents through the screening of combinatorial libraries which function by inhibiting the binding and localization of proteinase MMP2 to integrin αvβ3 [J].
Boger, DL ;
Goldberg, J ;
Silletti, S ;
Kessler, T ;
Cheresh, DA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (07) :1280-1288
[10]   ANTIINTEGRIN ALPHA-V-BETA-3 BLOCKS HUMAN BREAST-CANCER GROWTH AND ANGIOGENESIS IN HUMAN SKIN [J].
BROOKS, PC ;
STROMBLAD, S ;
KLEMKE, R ;
VISSCHER, D ;
SARKAR, FH ;
CHERESH, DA .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (04) :1815-1822
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