THE POTENTIAL ROLE OF BASIC FIBROBLAST, GROWTH-FACTOR IN THE TRANSFORMATION OF CULTURED PRIMARY HUMAN FETAL ASTROCYTES AND THE PROLIFERATION OF HUMAN GLIOMA (U-87) CELLS
THE POTENTIAL ROLE OF BASIC FIBROBLAST, GROWTH-FACTOR IN THE TRANSFORMATION OF CULTURED PRIMARY HUMAN FETAL ASTROCYTES AND THE PROLIFERATION OF HUMAN GLIOMA (U-87) CELLS
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DOI：
10.1227/00006123-199510000-00017
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发表时间：
1995-10-01
期刊：
影响因子：
4.8
通讯作者：
BREM, S
中科院分区：
文献类型：
--
作者：
GATELY, S;SOFF, GA;BREM, S
碱性成纤维细胞生长因子（bFGF）是一种有效的刺激血管生成，增殖和人类胶质瘤的侵袭。为了检验bFGF在人类神经胶质瘤恶性表型的发展中是重要的这一假设，在原代人类胎儿星形胶质细胞和已建立的人类神经胶质瘤细胞系中对bFGF表达进行了前瞻性调节。用表达bFGF的载体转染胎儿星形胶质细胞，通过添加分泌信号肽序列进行修饰。这些碱性成纤维细胞生长因子星形胶质细胞克隆在体外研究表现出锚定独立的增长，接触抑制的损失，并减少胶质细胞酸性蛋白的免疫反应性，与细胞转化的变化一致。为了分析bFGF表达的抑制，将硫代磷酸化bFGF反义寡脱氧核苷酸加入到U-87人胶质瘤细胞系的培养物中。10 μ mol/L和20 μ mol/L对U-87细胞增殖的抑制率分别为对照组的70.6 ± 0.4%和53.2 ± 5.6%（P < 0.05）。7.0-和4.0-双酶bFGF信使核糖核酸转录物在暴露于反义寡核苷酸后均减少，细胞相关bFGF蛋白减少44%。正义寡脱氧核苷酸，阴性对照，不能抑制U-87增殖。这些数据支持的概念，bFGF的表达可能是一个关键的事件，在神经胶质瘤的发生，可能是必要的人类胶质瘤的持续增长。
BASIC FIBROBLAST GROWTH factor (bFGF) is a potent stimulator of angiogenesis, proliferation, and invasion in human gliomas. To test the hypothesis that bFGF is important in the development of the malignant phenotype of human gliomas, bFGF expression was prospectively modulated in primary human fetal astrocytes and in an established human glioma cell line. Fetal astrocytes were transfected with a vector expressing bFGF modified by the addition of a secretory signal peptide sequence. Two of these bFGF astrocyte clones examined in vitro demonstrated anchorage-independent growth, loss of contact inhibition, and decreased glial fibrillary acidic protein immunoreactivity, changes consistent with cellular transformation. To analyze the inhibition of bFGF expression, phosphore-thioated bFGF antisense oligodeoxynucleotides were added to cultures of the U-87 human glioma cell line. The U-87 cell proliferation was inhibited to 70.6 +/- 0.4% of control at 10 mu Lmol/L and to 53.2 +/- 5.6% of control at 20 mu mol/L (P < 0.05). Both the 7.0- and 4.0-kilobase bFGF messenger ribonucleic acid transcripts were reduced after exposure to the antisense oligodeoxynucleotide, and cell-associated bFGF protein was reduced by 44%. The sense oligodeoxynucleotide, a negative control, failed to inhibit U-87 proliferation. These data support the concept that bFGF expression could be a key event in glial tumorigenesis that may be necessary for the sustained growth of human gliomas.