B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells
B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells
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B7-H1 与恶性级别神经胶质瘤相关，但并不只在肿瘤干细胞样细胞上表达
DOI：
10.1215/15228517-2009-014
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发表时间：
2009-12-01
期刊：
影响因子：
15.9
通讯作者：
Zhou, Liang Fu
中科院分区：
文献类型：
--
作者：
Yao, Yu;Tao, Ran;Zhou, Liang Fu
人类胶质母细胞瘤以其干扰有效抗肿瘤免疫反应的能力而闻名。B7- h1是B7家族的第三个成员，在肿瘤免疫逃避中发挥重要作用。近年来的研究表明，脑肿瘤干样细胞（TSCs）参与肿瘤发生和放射抵抗。然而，B7-H1与脑TSCs临床行为的关系尚不清楚。在本研究中，我们报道B7-H1与星形细胞肿瘤的恶性程度相关。B7-H1在肿瘤生长边缘显著上调。免疫染色和流式细胞术分析表明B7-H1主要在ki67阴性肿瘤细胞中表达。在体外，在有利于神经干细胞生长的培养基中培养的肿瘤能够形成球体，并表达神经干细胞/祖细胞标记物。这些细胞在分化培养基中能够分化成不同的神经系，表明这些细胞具有TSC特征。我们还发现B7-H1在cd133阳性干细胞上也有表达，但不局限于cd133阳性干细胞。有趣的是，我们发现cd133阴性的肿瘤细胞也有形成脑肿瘤的能力。我们的数据建立了负性共刺激分子B7-H1的表达与人类胶质瘤的恶性程度之间的相关性，这表明B7-H1可能是一种新的肿瘤标志物和治疗靶点，尽管它并不只在脑tsc上表达。神经肿瘤学11,757-766,2009(发表于神经肿瘤学[连续在线]，博士。D08-00272, 2009年3月5日URL http://neuro-oncology.dukejournals.org;DOI: 10.1215 / 15228517-2009-014)
Human glioblastoma is well known for its capacity to interfere with effective antitumor immune responses. B7-H1 is the third member of the B7 family that plays important roles in tumor immune evasion. Recent studies have shown that brain tumor stem-like cells (TSCs) contribute to tumorigenesis and radioresistance. However, the relationship between B7-H1 and the clinical behavior of brain TSCs remains unclear. In the present study, we report that B7-H1 is correlated with the malignancy grade of astrocyte tumors. B7-H1 was significantly upregulated at the growing edge of the tumors. Immunostaining and flow cytometric analysis indicate that B7-H1 was expressed primarily by Ki67-negative tumor cells. In vitro, tumors cultured under medium favoring the growth of neural stern cells were able to form spheres, along with expression of neural stem/progenitor cell markers. These cells were able to differentiate into different neural lineages when cultured in differentiation medium, indicating that these cells have TSC characteristics. We also found that B7-H1 was expressed, but not exclusively on CD133-positive stem cells. Interestingly, we found that CD133-negative tumor cells also had the capacity to form brain tumors. Our data establish a correlation between the expression of the negative costimulatory molecule B7-H1 and the malignancy grade of human gliomas, suggesting that B7-H1 may be a novel tumor marker and target for therapy, although it is not expressed exclusively on brain TSCs. Neuro-Oncology 11, 757-766, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00272, March 5, 2009. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2009-014)