期刊
BLOOD
卷 116, 期 18, 页码 3677-3680出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-06-291930
关键词
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类别
资金
- Istituto Superiore di Sanita
- Ministero dell'Istruzione
- Universita e Ricerca (Centro di Eccellenza per l'Innovazione Diagnostica e Terapeutica)
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [MFAG 9161]
- Fondazione Berlucchi
- Fondazione Cariplo [2008-2264]
- Swiss National Science Foundation [3100A-116507]
- Oncosuisse [OC2 01200-08-2007]
The bone morphogenic protein antagonist gremlin is expressed during embryonic development and under different pathologic conditions, including cancer. Gremlin is a proangiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-beta proteins and the angiogenic vascular endothelial growth factors (VEGFs). Here, we demonstrate that gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals, in a bone morphogenic protein-independent manner. Similar to VEGF-A, gremlin activates VEGFR2 in endothelial cells, leading to VEGFR2-dependent angiogenic responses in vitro and in vivo. Gremlin thus represents a novel proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization. (Blood. 2010;116(18):3677-3680)
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