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Titolo:
Two independent mechanisms essential for tumor angiogenesis: Inhibition ofhuman melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway
Autore:
Siemeister, G; Schirner, M; Weindel, K; Reusch, P; Menrad, A; Marme, D; Martiny-Baron, G;
Indirizzi:
Schering AG, Expt Oncol, Res Labs, D-13342 Berlin, Germany Schering AG Berlin Germany D-13342 ol, Res Labs, D-13342 Berlin, Germany Tumor Biol Ctr, Inst Mol Med, D-79106 Freiburg, Germany Tumor Biol Ctr Freiburg Germany D-79106 l Med, D-79106 Freiburg, Germany
Titolo Testata:
CANCER RESEARCH
fascicolo: 13, volume: 59, anno: 1999,
pagine: 3185 - 3191
SICI:
0008-5472(19990701)59:13<3185:TIMEFT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLOOD-VESSEL FORMATION; TYROSINE KINASE; IN-VIVO; EMBRYONIC ANGIOGENESIS; SOLUBLE RECEPTOR; VEGF-C; EXPRESSION; GENE; ANGIOPOIETIN-1; VASCULOGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Siemeister, G Schering AG, Expt Oncol, Res Labs, Mullerstr 178, D-13342 Berlin, Germany Schering AG Mullerstr 178 Berlin Germany D-13342 n, Germany
Citazione:
G. Siemeister et al., "Two independent mechanisms essential for tumor angiogenesis: Inhibition ofhuman melanoma xenograft growth by interfering with either the vascular endothelial growth factor receptor pathway or the Tie-2 pathway", CANCER RES, 59(13), 1999, pp. 3185-3191

Abstract

Protein ligands and receptor tyrosine kinases that specifically regulate endothelial cell function are mainly involved in physiological as well as indisease-related angiogenesis. These ligand/receptor systems include the vascular endothelial growth factor (VEGF) and the angiopoietin (Ang) families, and their receptors, the VEGF receptor family and the tyrosine kinase with immunoglobulin-like and epidermal growth factor homology domains (Tie) family. In the present study, the contribution of these endothelium-specific ligand/receptor systems to tumor angiogenesis was evaluated. A375v human melanoma cells, which express at least the angiogenic growth factors VEGF, VEGF-C, and Ang-1, were stably transfected to overexpress the extracellular ligand-binding domains of the endothelium-specific receptor tyrosine kinasesfats-like tyrosine kinase-1 (Flt-1), Flt-4, Tie-1, and Tie-2, respectively. In vitro proliferation and colony formation assays confirmed that expression of the extracellular receptor domains inhibited neither tumor cell mitogenesis nor the ability to produce anchorage-independent growth. Nude mousexenografts revealed that interference with either the VEGF receptor pathway or the Tie-2 pathway resulted in a significant inhibition of tumor growthand tumor angiogenesis. In contrast, interference with the Flt-4 pathway or the Tie-1 pathway was without significant effect. Our results show that both the VEGF receptor pathway and the Tie-2 pathway are essential for A375vmelanoma xenograft growth. The inhibition of the VEGF receptor pathway cannot be compensated by the Tie-2 pathway, nor vice versa, These findings suggest that the VEGF receptor pathway and the Tie-2 pathway have to be considered as two independent mediators essential for the process of in vivo angiogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 12:25:08