期刊
CANCER CELL
卷 28, 期 2, 页码 225-239出版社
CELL PRESS
DOI: 10.1016/j.ccell.2015.07.002
关键词
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资金
- Ministero lstruzione, Universita e Ricerca (FIRB project) [RBAP11H2R9 2011]
- Associazione Italians Ricerca sul Cancro (AIRC) [14395, 1G 15420]
- Fondazione Cariplo (Premio Fondazione Cariplo per la Ricerca di Frontiera) [2011.1800]
- Fondazione Italiana per la Ricerca sul Cancro fellowships
- Fondazione Veronesi fellowship
- Fondazione Antonio De Marco grant
The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance, and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. Here we demonstrate that human PTX3 overexpression in transgenic mice driven by the Tie2 promoter inhibits tumor growth, angiogenesis, and metastasis in heterotopic, orthotopic, and autochthonous FGF-dependent tumor models. Using pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2, we identified a small-molecule chemical (NSC12) that acts as an extracellular FGF trap with significant implications in cancer therapy.
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