Correlation between glioblastoma stem-like cells and tumor vascularization
Correlation between glioblastoma stem-like cells and tumor vascularization
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DOI：
10.3892/or.2011.1484
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Li, Ming Wu
中科院分区：
文献类型：
--
作者：
He, Hu;Niu, Chao Shi;Li, Ming Wu
多形性胶质母细胞瘤（GBM）是最致命的脑肿瘤类型。异常、功能失调的肿瘤血管和胶质母细胞瘤干细胞样细胞（GSCs）的形成被认为是无法有效治疗这些肿瘤的主要原因。我们对70例胶质母细胞瘤标本进行免疫组化和双免疫荧光染色分析。采用形态计量学方法对脑肿瘤干细胞标记物CD133和Nestin在石蜡切片中的免疫组化表达进行分析。在所有GBM样本中，CD133或Nestin在肿瘤和内皮细胞中表达。双免疫荧光染色显示两种不同标记的GSCs在CD31（+）血管周围聚集，内皮细胞和GSCs中存在CD133/CD31或Nestin/CD31共表达。此外，血管内皮生长因子（VEGF）和内皮标志物CD31在GSCs中共表达。因此，GSCs不仅具有明显的血管周围分布，而且具有向内皮细胞分化的能力。我们证明了GSCs通过内皮细胞分化直接促进肿瘤血管的形成。GSCs与肿瘤血管化不仅在区域分布上密切相关，而且在生物学功能上也密切相关。这些发现描述了肿瘤血管形成的新机制，可能为脑肿瘤靶向治疗提供新的见解。
Glioblastoma multiforme (GBM) is the most lethal type of brain tumor. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the inability to treat these tumors effectively. We analyzed 70 glioblastoma samples by immunohistochemistry and double immunofluorescence staining. The immunohistochemical expression of the putative brain tumor stem cell markers CD133 and Nestin in paraffin sections was analyzed using morphometry. In all GBM samples, CD133 or Nestin was expressed in tumor and endothelial cells. Double immunofluorescence stainings showed that the two different marked GSCs were found accumulated around the CD31(+) blood vessels and CD133/CD31 or Nestin/CD31 co-expression was found in the endothelial cells and GSCs. Furthermore, the vascular endothelial growth factor (VEGF) and the endothelial marker CD31 were co-expressed in GSCs. Therefore, GSCs not only showed distinct perivascular distribution but were capable of differentiating into endothelial cells. We demonstrate that GSCs contribute directly to the tumor vasculature by endothelial cell differentiation. GSCs and tumor vascularization are closely related to each other, not only in the regional distribution but also in biological function. These findings describe a new mechanism for tumor vasculogenesis and may provide new insights for targeted therapy against brain tumors.