Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Neuro Oncol. 2009 Dec;11(6):757-66. 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 stem 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.
人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,在肿瘤免疫逃逸中发挥重要作用。最近的研究表明,脑肿瘤干细胞样细胞(TSCs)有助于肿瘤发生和放射抵抗。然而,B7-H1 与脑 TSCs 的临床行为之间的关系尚不清楚。在本研究中,我们报告 B7-H1 与星形细胞瘤的恶性程度相关。B7-H1 在肿瘤的生长边缘明显上调。免疫组化和流式细胞术分析表明,B7-H1 主要由 Ki67 阴性肿瘤细胞表达。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/祖细胞标志物。这些细胞在分化培养基中培养时能够分化为不同的神经谱系,表明这些细胞具有 TSC 特征。我们还发现 B7-H1 表达,但不仅限于 CD133 阳性干细胞。有趣的是,我们发现 CD133 阴性肿瘤细胞也具有形成脑肿瘤的能力。我们的数据建立了负共刺激分子 B7-H1 的表达与人胶质母细胞瘤恶性程度之间的相关性,表明 B7-H1 可能是一种新的肿瘤标志物和治疗靶点,尽管它并非仅表达于脑 TSCs 上。