Ke L D, Shi Y X, Im S A, Chen X, Yung W K
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 2000 Jun;6(6):2562-72.
Tumor growth is partially dependent on angiogenesis, a process that relies on angiogenic factors. Tumorigenicity of cancer cells is thought to be associated with the production of various angiogenic factors that stimulate or inhibit the rate of endothelial cell migration and proliferation. However, the relative importance of specific individual factors originally studied in cancer cell lines has yet to be determined in vivo. In this study, we examined seven human glioma cell lines for dynamic changes of two major angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), and for doubling time and tumorigenicity in nude mice. Various correlation studies demonstrated that in these glioma cell lines, VEGF expression correlated well with RBC density in tumor sections (r2 = 0.804) and with average tumor weight (r2 = 0.987). In contrast, bFGF expression in the observed glioma cell lines did not correlate with tumorigenicity (r2 = 0.001) or with VEGF expression (r2 = 0.255). Furthermore, there was no correlation between doubling time and tumorigenicity in these cell lines (r2 = 0.160). Taken together, these results suggest that VEGF plays a major role in glioma formation and that down-regulation of VEGF, rather than bFGF, would be a more effective choice for glioma gene therapy.
肿瘤生长部分依赖于血管生成,这一过程依赖于血管生成因子。癌细胞的致瘤性被认为与多种血管生成因子的产生有关,这些因子可刺激或抑制内皮细胞迁移和增殖的速率。然而,最初在癌细胞系中研究的特定个体因子的相对重要性尚未在体内得到确定。在本研究中,我们检测了七种人胶质瘤细胞系中两种主要血管生成因子,即碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)的动态变化,以及在裸鼠中的倍增时间和致瘤性。各种相关性研究表明,在这些胶质瘤细胞系中,VEGF表达与肿瘤切片中的红细胞密度(r2 = 0.804)以及平均肿瘤重量(r2 = 0.987)密切相关。相比之下,在观察到的胶质瘤细胞系中,bFGF表达与致瘤性(r2 = 0.001)或VEGF表达(r2 = 0.255)均无相关性。此外,这些细胞系中的倍增时间与致瘤性之间也没有相关性(r2 = 0.160)。综上所述,这些结果表明VEGF在胶质瘤形成中起主要作用,并且下调VEGF而非bFGF将是胶质瘤基因治疗更有效的选择。