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Titolo:
Differential inhibition of tumor angiogenesis by TIE2 and vascular endothelial growth factor receptor-2 dominant-negative receptor mutants
Autore:
Stratmann, A; Acker, T; Burger, AM; Amann, K; Risau, W; Plate, KH;
Indirizzi:
Univ Freiburg, Sch Med, Dept Neuropathol, Freiburg, Germany Univ FreiburgFreiburg Germany Med, Dept Neuropathol, Freiburg, Germany Univ Erlangen Nurnberg, Sch Med, Inst Pathol, Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany Inst Pathol, Erlangen, Germany Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany Univ Freiburg Freiburg Germany iburg, Tumor Biol Ctr, Freiburg, Germany Max Planck Inst Physiol & Clin Res, Dept Mol Cell Biol, D-6350 Bad Nauheim, Germany Max Planck Inst Physiol & Clin Res Bad Nauheim Germany D-6350 m, Germany
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 3, volume: 91, anno: 2001,
pagine: 273 - 282
SICI:
0020-7136(20010201)91:3<273:DIOTAB>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
TYROSINE KINASE; BREAST-CANCER; IN-VIVO; FACTOR EXPRESSION; UP-REGULATION; EMBRYONIC ANGIOGENESIS; PROGNOSTIC INDICATOR; RAT GLIOMA; ANGIOPOIETIN-1; MECHANISMS;
Keywords:
tumor angiogenesis; tyrosine kinase receptors; vascular endothelial growth factor; TIE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Plate, KH FAU Erlangen Nurnberg, Inst Pathol, Krankenhausstr 8-10, D-91054Erlangen,Germany FAU Erlangen Nurnberg Krankenhausstr 8-10 Erlangen Germany D-91054
Citazione:
A. Stratmann et al., "Differential inhibition of tumor angiogenesis by TIE2 and vascular endothelial growth factor receptor-2 dominant-negative receptor mutants", INT J CANC, 91(3), 2001, pp. 273-282

Abstract

Tumor growth is angiogenesis-dependent. Current evidence suggests that vascular endothelial growth factor (VEGF), a major regulator of embryonic and hypoxia-mediated angiogenesis, is necessary for tumor angiogenesis. VEGF isexpressed in tumor cells in vivo, and its tyrosine kinase receptors VEGFR-1 and VEGFR-2 are up-regulated in the tumor endothelium. A second endothelial cell-specific ligand/receptor tyrosine kinase system, consisting of the tie2 receptor, its activating ligand angiopoietin-1 and the inhibitory ligand angiopoietin-2, has been characterized. We have examined 6 human primarybreast-cancer samples and 4 murine breast-cancer cell lines (M6363, M6378,M6444, M6468), transplanted into nude mice, by in situ hybridization and/or Northern analysis. Expression of angiopoietin-1, angiopoietin-2 and tie2 was compared to VEGF and VEGFR-2 expression. Human tumors expressed VEGFR-2and tie2 but varied considerably in VEGF and angiopoietin-1/-2 expression. In the murine tumor models, we observed high heterogeneity of receptor andligand expression. M6363 and M6378 tumors were analyzed in detail because they showed different expression of components of the tie2/angiopoietin signaling system. M6363 tumors expressed VEGF, VEGFR-2 and angiopoietin-1 but not tie2 or angiopoietin-1, suggesting activation of VEGFR-2 and inhibitionof tie2 signaling pathways, whereas M6378 tumors expressed VEGF, VEGFR-2, tie2 and angiopoietin-1 but little angiopoietin-2, suggesting activation ofboth VEGFR-2 and tie2 signaling pathways. In viva studies using truncated dominant-negative tie2 and VEGFR-2 mutants revealed inhibition of M6363 tumor growth by 15% (truncated tie2) and 36% (truncated VEGFR-2), respectively. In contrast, M6378 tumor growth was inhibited by 57% (truncated tie2) and47% (truncated VEGFR-2), respectively. These findings support the hypothesis that tumor angiogenesis is dependent on VEGFR-2 but suggest that, in addition, tie2-dependent pathways of tumor angiogenesis may exist. For adequate application of angiogenesis inhibitors in tumor patients, analysis of prevailing angiogenesis pathways may be a prerequisite. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 07:04:21