Nomura M, Yamagishi S, Harada S, Yamashima T, Yamashita J, Yamamoto H
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
J Neurooncol. 1998 Nov;40(2):123-30. doi: 10.1023/a:1006198422718.
To investigate the relationship between placenta growth factor (PlGF) and brain tumor angiogenesis, we screened 36 primary and 3 metastatic brain tumors. We examined the expression of PlGF mRNA with respect to vasculature of various tumors which was determined by preoperative angiography. The expression of genes of the other angiogenic factors, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was also tested, and compared to that of PlGF. The primary tumors consisted of 16 meningiomas, 7 gliomas, 7 schwannomas, 4 pituitary adenomas, 1 germinoma, and 1 choriocarcinoma. Using a quantitative reverse transcription-polymerase chain reaction, the mRNA for PlGF149 and PlGF170 were detected in 25 out of 39 (64.1%) brain tumors. In primary brain tumors, PIGF mRNA was expressed in all the hypervascular tumors, but only in 5 of 16 hypovascular tumors (31.3%). None of the 3 metastatic hypervascular tumors expressed PlGF mRNA. The VEGF and bFGF mRNA expression was both detected in 87.2% of the tumors examined. We conducted hypoxic experiments with cultured U-251MG human glioma cells to determine the mechanism of PIGF gene regulation. As the atmospheric oxygen concentration was decreased, the PIGF mRNA level in the U-251MG cells was markedly increased. These results suggest that PIGF may contribute to the pathogenesis of brain tumor angiogenesis.
为了研究胎盘生长因子(PlGF)与脑肿瘤血管生成之间的关系,我们筛选了36例原发性脑肿瘤和3例转移性脑肿瘤。我们根据术前血管造影确定的各种肿瘤的脉管系统,检测了PlGF mRNA的表达。还检测了其他血管生成因子,血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的基因表达,并与PlGF进行比较。原发性肿瘤包括16例脑膜瘤、7例胶质瘤、7例神经鞘瘤、4例垂体腺瘤、1例生殖细胞瘤和1例绒毛膜癌。使用定量逆转录聚合酶链反应,在39例脑肿瘤中的25例(64.1%)中检测到PlGF149和PlGF170的mRNA。在原发性脑肿瘤中,PIGF mRNA在所有高血管肿瘤中均有表达,但在16例低血管肿瘤中仅5例(31.3%)表达。3例转移性高血管肿瘤均未表达PlGF mRNA。在所检测的肿瘤中,87.2%均检测到VEGF和bFGF mRNA表达。我们用培养的U-251MG人胶质瘤细胞进行了缺氧实验,以确定PIGF基因调控的机制。随着大气氧浓度的降低,U-251MG细胞中的PIGF mRNA水平显著升高。这些结果表明,PIGF可能参与脑肿瘤血管生成的发病机制。