Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Cancer Cell. 2015 Aug 10;28(2):225-39. doi: 10.1016/j.ccell.2015.07.002.
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.
成纤维细胞生长因子 (FGF)/成纤维细胞生长因子受体 (FGFR) 系统通过影响肿瘤生长、血管生成、耐药性和逃避抗血管内皮生长因子治疗，在癌症中发挥着至关重要的作用。可溶性模式识别受体长五聚体 3 (PTX3) 作为一种多 FGF 拮抗剂。在这里，我们证明了由 Tie2 启动子驱动的转基因小鼠中人类 PTX3 的过表达可抑制异位、原位和同源 FGF 依赖性肿瘤模型中的肿瘤生长、血管生成和转移。通过最小的 PTX3 衍生 FGF 结合五肽与 FGF2 相互作用的药效团建模，我们鉴定了一种小分子化学物质 (NSC12)，它作为细胞外 FGF 陷阱具有重要的癌症治疗意义。
Zotero 插件