Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1α in human glioblastoma
Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1α in human glioblastoma
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DOI：
10.1111/neup.12111
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发表时间：
2014-08-01
期刊：
影响因子：
2.3
通讯作者：
Rosemberg, Sergio
中科院分区：
文献类型：
--
作者：
Clara, Carlos Afonso;Marie, Suely K. N.;Rosemberg, Sergio
胶质母细胞瘤（GBM）是最常见和最具侵袭性的脑肿瘤，其特征是显著的血管生成，与侵袭性和预后不良直接相关。缺氧被认为是通过诱导激活血小板衍生生长因子（PDGF）和VEGF的缺氧诱导因子1-α（HIF-1 α）过表达而对血管生成的重要刺激。本研究旨在分析血小板源性生长因子C（PDGF-C）、血管内皮生长因子（VEGF）在胶质母细胞瘤（GBM）内皮细胞和肿瘤细胞中的表达及其与缺氧诱导因子1 α（HIF-1 α）表达的关系。应用组织芯片免疫组化技术对208例GBM进行研究。HIF-1 α、VEGF和PDGF-C的表达分别在184例（88.5%）、131例（63%）和160例（76.9%）肿瘤中观察到。通过CD 34、PDGF-C、VEGF和CD 105染色定量血管数量，中位数分别为20、16、5和6。HIF-1 α阳性或阴性表达的GBM显示CD 34的中位血管密度分别为30和14（P < 0.015）。HIF-1 α阳性表达与VEGF、PDGF-C表达相关（P < 0.001）。VEGF和PDGF-C在GBM肿瘤细胞胞浆中的表达具有显著相关性（P < 0.0001）。VEGF在肿瘤细胞中的表达与其在血管中的表达呈正相关（P < 0.0001）。具有PDGF-C和VEGF阳性表达的内皮细胞也为CD 105阳性，并且其核为Ki-67阳性，证实VEGF和PDGF-C的新血管生成和增殖影响。肿瘤细胞中VEGF核染色（P = 0.002）以及HIF-1 α和VEGF核染色（P = 0.005）与生存相关。总之，我们目前发现的GBM肿瘤细胞和血管中PDGF-C与VEGF的伴随上调进一步加强了使用联合抗血管生成方法的益处，以潜在地改善GBM的治疗反应。
Glioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1 alpha) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGFin endothelial and tumor cells of GBM and their relation to HIF-1 alpha expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1 alpha, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1 alpha showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1 alpha was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1 alpha and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM.