阶段特异性胚胎抗原 4 作为多形性胶质母细胞瘤和其他癌症的潜在治疗靶点。
Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers.
机构信息
Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
出版信息
Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2482-7. doi: 10.1073/pnas.1400283111. Epub 2014 Feb 3.
Abstract
Glioblastoma multiforme (GBM), the grade IV astrocytoma, is the most common and aggressive brain tumor in adults. Despite advances in medical management, the survival rate of GBM patients remains poor, suggesting that identification of GBM-specific targets for therapeutic development is urgently needed. Analysis of several glycan antigens on GBM cell lines revealed that eight of 11 GBM cell lines are positive for stage-specific embryonic antigen-4 (SSEA-4), and immunohistochemical staining confirmed that 38/55 (69%) of human GBM specimens, but not normal brain tissue, were SSEA-4(+) and correlated with high-grade astrocytoma. In addition, an SSEA-4-specific mAb was found to induce complement-dependent cytotoxicity against SSEA-4(hi) GBM cell lines in vitro and suppressed GBM tumor growth in mice. Because SSEA-4 is expressed on GBM and many other types of cancers, but not on normal cells, it could be a target for development of therapeutic antibodies and vaccines.
摘要
多形性胶质母细胞瘤（GBM）是四级星形细胞瘤，是成人中最常见且侵袭性最强的脑肿瘤。尽管在医学治疗方面取得了进展，但 GBM 患者的生存率仍然很差，这表明迫切需要确定用于治疗开发的 GBM 特异性靶标。对 GBM 细胞系上的几种糖抗原进行分析显示，11 个 GBM 细胞系中有 8 个呈阶段特异性胚胎抗原-4（SSEA-4）阳性，免疫组织化学染色证实 55 个人类 GBM 标本中有 38 个（69%）为 SSEA-4（+），与高级别星形细胞瘤相关。此外，发现一种 SSEA-4 特异性 mAb 可在体外诱导针对 SSEA-4（高）GBM 细胞系的补体依赖性细胞毒性，并抑制小鼠中的 GBM 肿瘤生长。因为 SSEA-4 存在于 GBM 和许多其他类型的癌症中，但不存在于正常细胞中，所以它可能是开发治疗性抗体和疫苗的靶标。
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