Department of Neurosurgery of Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
Mol Carcinog. 2012 Jul;51(7):586-95. doi: 10.1002/mc.20829. Epub 2011 Jul 14.
Survivin is involved in multiple signaling mechanisms in tumor maintenance, and accumulated studies elucidate that knockdown of survivin in endothelial cells could inhibit angiogenesis; however, the role of survivin in tumor cells to regulate tumor-derived angiogenesis remains largely unclear. In the present study 80 cases of brain glioma were chosen and protein expressions of survivin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in glioma cells were investigated by immunohistochemistry (IHC). Human umbilical vein endothelial cells (HUVEC) were cocultured with human glioma U251 wild-type cells, U251 cells survivin silenced, SHG44 wild-type cells, and SHG44 survivin-overexpressing cells, respectively. The proliferation and migration of HUVEC were evaluated by MTT assay and transwell chamber assay. The microvessels density (MVD) marked by CD31 expression in vascular endothelial cells in glioma xenografts in nude mice was detected by IHC. VEGF, bFGF, and PDGF in the aforementioned cells were detected by quantitive PCR (qPCR), Western blot, ELISA, and IHC in vitro and in vivo. The results showed that VEGF immunoreactivity score (IRS), bFGF IRS, and PDGF IRS were all positively correlated with survivin IRS in gliomas, respectively (P < 0.01). Survivin in human glioma cells could significantly promote the proliferation and migration of HUVEC and increase MVD, which could be contributed to survivin-dependent burst of VEGF and bFGF expression, followed by increase of tumor growth and proliferation. In summary, survivin, through upregulation of VEGF and bFGF, plays an essential role during glioma angiogenesis.
Survivin 参与肿瘤维持的多种信号机制，大量研究阐明，内皮细胞中 survivin 的敲低可抑制血管生成；然而，survivin 在肿瘤细胞中调节肿瘤源性血管生成的作用在很大程度上仍不清楚。本研究选择 80 例脑胶质瘤患者，采用免疫组织化学（IHC）方法检测胶质瘤细胞中 survivin、血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和血小板衍生生长因子（PDGF）的蛋白表达。分别将人脐静脉内皮细胞（HUVEC）与野生型人胶质瘤 U251 细胞、沉默 survivin 的 U251 细胞、SHG44 野生型细胞和过表达 survivin 的 SHG44 细胞共培养，通过 MTT 法和 Transwell 小室法评估 HUVEC 的增殖和迁移。通过免疫组化法检测裸鼠胶质瘤异种移植瘤中 CD31 标记的血管内皮细胞的微血管密度（MVD）。通过体外和体内 qPCR、Western blot、ELISA 和 IHC 检测上述细胞中 VEGF、bFGF 和 PDGF 的表达。结果显示，VEGF 免疫反应评分（IRS）、bFGF IRS 和 PDGF IRS 与胶质瘤中的 survivin IRS 均呈正相关（P<0.01）。人胶质瘤细胞中的 survivin 可显著促进 HUVEC 的增殖和迁移，增加 MVD，这可能归因于 survivin 依赖性 VEGF 和 bFGF 表达的爆发，随后肿瘤生长和增殖增加。总之，survivin 通过上调 VEGF 和 bFGF，在胶质瘤血管生成中发挥重要作用。
