Alvarez J A, Baird A, Tatum A, Daucher J, Chorsky R, Gonzalez A M, Stopa E G
Department of Pathology, SUNY Health Science Center, Syracuse.
Mod Pathol. 1992 May;5(3):303-7.
Fibroblast growth factors (FGFs) are widely recognized as a family of molecules that can influence cell proliferation and tissue neovascularization. Although the basic form of FGF (bFGF) has been found to enhance the growth of primary cell cultures made from human glial tumors, its exact role in vivo has been unclear. Likewise, vascular endothelial growth factor (VEGF) is a newly discovered addition to the growing list of angiogenic factors but, unlike bFGF, VEGF has a unique specificity for endothelial cells and possesses the properties required for secretion. In this study, we localized both basic FGF and VEGF in human gliomas to assess their possible role in the pathogenesis of these neoplasms. Retrospective analysis was performed using glial neoplasms that were fixed in 10% neutral buffered formalin and embedded in paraffin. The immunocytochemical procedures were performed using specific polyclonal antibodies raised against the amino terminus of bFGF and VEGF, respectively. Immunoreactive (IR) basic FGF was localized in normal, reactive, and neoplastic astrocytes as well as selected populations of normal neurons. IR VEGF, in contrast, was present primarily in neurons of normal brain, but was also found in both reactive and neoplastic astrocytes. In adjacent 4-microns tissue sections, strong immunoreactivity for VEGF and bFGF was found within the same populations of cells. In areas of endothelial proliferation, the strongest immunoreactivity for both growth factors was found within large anaplastic astrocytes that surrounded abnormal blood vessels. Our data support the hypothesis that VEGF may complement the actions of basic FGF in glial neoplasia.
成纤维细胞生长因子（FGFs）被广泛认为是一类能够影响细胞增殖和组织新血管形成的分子家族。尽管已发现碱性成纤维细胞生长因子（bFGF）的基本形式可促进源自人神经胶质瘤的原代细胞培养物的生长，但其在体内的确切作用尚不清楚。同样，血管内皮生长因子（VEGF）是不断增加的血管生成因子列表中的新成员，但与bFGF不同，VEGF对内皮细胞具有独特的特异性，并具有分泌所需的特性。在本研究中，我们对人神经胶质瘤中的碱性成纤维细胞生长因子和血管内皮生长因子进行定位，以评估它们在这些肿瘤发病机制中的可能作用。使用固定于10%中性缓冲福尔马林中并包埋于石蜡中的神经胶质瘤进行回顾性分析。免疫细胞化学程序分别使用针对bFGF和VEGF氨基末端产生的特异性多克隆抗体进行。免疫反应性（IR）碱性成纤维细胞生长因子定位于正常、反应性和肿瘤性星形胶质细胞以及选定的正常神经元群体中。相比之下，IR VEGF主要存在于正常脑的神经元中，但也在反应性和肿瘤性星形胶质细胞中发现。在相邻的4微米组织切片中，在相同的细胞群体中发现了对VEGF和bFGF的强免疫反应性。在内皮细胞增殖区域，在围绕异常血管的大间变性星形胶质细胞中发现了两种生长因子最强的免疫反应性。我们的数据支持这样的假设，即VEGF可能在神经胶质瘤形成中补充碱性成纤维细胞生长因子的作用。
