SIGNIFICANCE OF ANGIOGENESIS IN TUMOR PROGRESSION AND METASTASIS
SIGNIFICANCE OF ANGIOGENESIS IN TUMOR PROGRESSION AND METASTASIS
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DOI：
10.1016/0959-8049(95)00169-j
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发表时间：
1995-07-01
影响因子：
8.4
通讯作者：
BIKFALVI, A
中科院分区：
文献类型：
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作者：
BIKFALVI, A
血管生成被定义为血管新生，通常起源于毛细血管。这一现象在发育过程中以及在几种生理和/或病理条件下都很重要。近年来，在分子水平上对这种现象的理解已经取得了进展。这包括识别有效的血管生成因子，评价蛋白酶的作用，细胞外基质的重要性，以及内皮细胞信号转导途径的新特征。血管生成的两个重要参与者是成纤维细胞生长因子(FGF)和转化生长因子-β(TGF-β)家族的分子。在我们的实验室里，我们已经广泛地研究了主要的成纤维细胞生长因子原型-2和转化生长因子-β1的作用和作用机制。之前已经描述了不同的成纤维细胞生长因子-2的不同亚型，与核相关的高分子量形式和胞浆中的18 kDa碱性成纤维细胞生长因子。这两种形式的成纤维细胞生长因子-2在内源性表达时也表现出不同的功能。转化生长因子-β是由纤溶酶依赖和非纤溶酶依赖的途径形成的潜在复合体。除了巨噬细胞外，纤溶酶依赖的途径需要共培养条件、尿激酶以及通过甘露糖-6-磷酸受体和转谷氨酰胺酶在细胞表面聚集转化生长因子-β。其他重要的血管生成调节因子包括血管内皮生长因子(VEGF)和血管抑素。肿瘤血管生成因子的性质尚不确定，但几种已识别和尚未识别的血管生成因子可能协同作用。人们希望从这些分子研究中衍生出一种癌症的血管抑制治疗方法。
Angiogenesis is defined as a vascular neoformation usually of capillary origin. This phenomenon is important during development and under several physiological and or pathological conditions. In recent years, progress has been made to understand this phenomenon at the molecular level. This includes the identification of potent angiogenic factors, the appreciation of the role of proteases, the importance of the extracellular matrix, and the emerging characterisation of signal transduction pathways in endothelial cells. Two important participants in angiogenesis are molecules from the fibroblast growth factor (FGF) and the transforming growth factor-beta (TGF-beta) family. In our laboratory, we have extensively studied the roles and mechanisms of action of the major FGF prototype, FGF-2 and of the TGF-beta member, TGF-beta 1. Different isoforms of FGF-2 have been previously described, a high molecular weight (HMW) form associated with the nucleus and 18 kDa bFGF that is cytoplasmic. These two forms of FGF-2 also exhibit different functions when expressed endogenously. TGF-beta is formed from a latent complex by plasmin-dependent and plasmin-independent pathways. With the exception of macrophages, the plasmin-dependent pathway requires coculture conditions, urokinase, and the concentration of TGF-beta on the cell surface by the mannose-6-phosphate receptor and transglutaminase. Other important angiogenic modulators include vascular endothelial growth factor (VEGF) and angiostatin. The nature of the tumour angiogenesis factor is not yet known with certainty, but several identified and not yet identified angiogenic factors may act in concert. It is hoped that an angiostatic treatment for cancer will be derived from these molecular studies.