The fibroblast growth factor-binding protein FGF-BP
The fibroblast growth factor-binding protein FGF-BP
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DOI：
10.1016/j.biocel.2005.10.017
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Aigner, Achim
中科院分区：
文献类型：
--
作者：
Abuharbeid, Shaker;Czubayko, Frank;Aigner, Achim
成纤维细胞生长因子(FGFs)是细胞迁移、增殖和分化的重要调节因子，在胚胎发育和伤口愈合过程中，以及在肿瘤生长和肿瘤血管生成等多种病理条件下，FGFs是细胞迁移、增殖和分化的重要调节因子。由于肝素结合的成纤维细胞生长因子与硫酸肝素蛋白多糖紧密结合，因此被困在细胞外基质中，通过成纤维细胞生长因子结合蛋白(FGFBP)的作用来释放它们是成纤维细胞生长因子生物活化的关键步骤之一。成纤维细胞生长因子-BP的表达具有高度的组织特异性，并受到不同启动子元件的严格调控。除了在胚胎发育和伤口愈合中的作用外，成纤维细胞生长因子-BP在一些肿瘤中表达上调，尤其与肿瘤形成的早期阶段有关，在肿瘤形成的早期，血管生成起着关键作用。与此同时，在一些小鼠肿瘤模型中，通过核酶或RNA干扰(RNAi)靶向FGF-BP可以消除或减少肿瘤生长和肿瘤血管生成。这表明，成纤维细胞生长因子BP对肿瘤生长具有限速作用，是一种血管生成开关分子，在抗肿瘤治疗中是一种越来越有前途的靶向分子。(C)2005爱思唯尔有限公司。保留所有权利。
Fibroblast growth factors (FGFs) are important regulators of cell migration, proliferation and differentiation, e.g., during embryogenesis and wound healing, and under several pathological conditions including tumor growth and tumor angiogenesis. Since heparin-binding FGFs are tightly bound to heparansulfate proteoglycans, and therefore, trapped in the extracellular matrix, their release through the action of an FGF-binding protein (FGF-BP) is one of the critical steps in FGF bioactivation. FGF-BP expression is highly tissue specific and strictly regulated through different promoter elements. Besides its role in embryogenesis and wound healing, FGF-BP is upregulated in several tumors and it is associated especially with early stages of tumor formation, where angiogenesis plays a critical role. Concomitantly, in several mouse tumor models, targeting of FGF-BP by ribozymes or RNA interference (RNAi) abolishes or reduces tumor growth and tumor angiogenesis. This indicates that FGF-BP can be rate-limiting for tumor growth and serves as an angiogenic switch molecule, and that it represents an increasingly promising target molecule in anti-tumor therapy. (c) 2005 Elsevier Ltd. All rights reserved.