CD90 is Identified as a Candidate Marker for Cancer Stem Cells in Primary High-Grade Gliomas Using Tissue Microarrays
CD90 is Identified as a Candidate Marker for Cancer Stem Cells in Primary High-Grade Gliomas Using Tissue Microarrays
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DOI：
10.1074/mcp.m111.010744
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发表时间：
2012-06-01
影响因子：
7
通讯作者：
Lubman, David M.
中科院分区：
文献类型：
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作者：
He, Jintang;Liu, Yashu;Lubman, David M.
尽管CD90已被确定为包括肝癌干细胞在内的多种干细胞的标志物，但CD90作为肿瘤干细胞标志物在胶质瘤中的潜在作用尚不清楚。为了解决这个问题，我们研究了CD90在15例多形性胶质母细胞瘤、19例WHO III级星形细胞瘤、13例WHO II级星形细胞瘤、3例WHO I级星形细胞瘤和8例正常脑组织中的表达。免疫组织化学分析显示，CD90在所有被检测的高级别胶质瘤(III级和GBM)中均有表达，而在低级别胶质瘤(I级和II级)和正常脑中几乎检测不到CD90的表达。CD90和CD133双重免疫荧光染色显示CD133(+)CSCs是体内GBM中CD90(+)细胞的一个亚群。流式细胞术分析CD90和CD133在GBM来源的干细胞样神经球中的表达在体外进一步证实了这一结论。分化后随着干细胞的丧失，CD90和CD133的表达水平均降低。极限稀释实验表明，CD90(+)/CD133(+)群体与CD90(+)/CD133(-)群体形成球体的能力相当，远高于CD90(-)/CD133(-)群体。我们还在组织芯片中进行了CD90和血管内皮细胞标志物CD31的双重染色，发现在高级别胶质瘤组织中，CD90(+)细胞聚集在肿瘤血管周围。这些结果表明，CD90不仅是高级别胶质瘤潜在的预后标志物，也是胶质瘤内CSCs的标志物，它存在于内皮细胞巢内，并可能通过分化为内皮细胞在肿瘤血管的形成中发挥关键作用。分子与细胞蛋白质组学11：10.1074/mcp.M111.010744，1-8,2012年。
Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBM) whereas it was barely detectable in low-grade gliomas (grade I and grade II) and normal brains. Double immunofluorescence staining for CD90 and CD133 in GBM tissues revealed that CD133(+) CSCs are a subpopulation of CD90(+) cells in GBMs in vivo. Flow cytometry analysis of the expression of CD90 and CD133 in GBM-derived stem-like neurospheres further confirmed the conclusion in vitro. The expression levels of both CD90 and CD133 were reduced along with the loss of stem cells after differentiation. Furthermore, the limiting dilution assay demonstrated that the sphere formation ability was comparable between the CD90(+)/CD133(+) and the CD90(+)/CD133(-) populations of GBM neurospheres, which is much higher than that of the CD90(-)/CD133(-) population. We also performed double staining for CD90 and a vascular endothelial cell marker CD31 in tissue microarrays which revealed that the CD90(+) cells were clustered around the tumor vasculatures in high-grade glioma tissues. These findings suggest that CD90 is not only a potential prognostic marker for high-grade gliomas but also a marker for CSCs within gliomas, and it resides within endothelial niche and may also play a critical role in the generation of tumor vasculatures via differentiation into endothelial cells. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.010744, 1-8, 2012.