Altered expression of α-dystroglycan subunit in human gliomas
Altered expression of α-dystroglycan subunit in human gliomas
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DOI：
10.4161/cbt.5.4.2546
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Petrucci, Tamara C.
中科院分区：
文献类型：
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作者：
Calogero, Antonella;Pavoni, Ernesto;Petrucci, Tamara C.
Dystroglycan（DG）是细胞外基质蛋白的膜受体，由来自共同前体的两个亚基α和β组成。在脑中，DG在神经元、胶质界膜、血管周围的星形胶质细胞终足和内皮细胞中表达。我们调查DG是否可能在脑肿瘤中发挥作用。免疫印迹和免疫荧光分析表明，虽然β-DG亚基存在，高度糖基化的α-DG亚基强烈减少手术来源的人胶质母细胞瘤活检，在低传代患者来源的文化和胶质瘤细胞系，U87 MG和A172 MG，但不是在所有的胶质瘤细胞系测试。肿瘤冰冻切片的免疫组化显示，α-DG的丢失仅限于肿瘤区域，而不是血管周围。DG的过表达降低了缺乏高度糖基化的α-DG亚基的胶质瘤细胞系的生长速度和集落形成效率。替莫唑胺存在下的克隆形成试验显示DG过表达和药物治疗之间的累加效应。我们的数据表明，DG可能参与原发性脑肿瘤的进展。
Dystroglycan (DG) is an integral membrane receptor of extracellular matrix proteins, composed of two subunits alpha and beta derived from a common precursor. In brain DG is expressed in neurons, glia limitans, astrocytic endfeet around vessels and endothelial cells. We investigate whether DG may play a role in brain tumors. Western blot and immunofluorescence analysis showed that, while beta-DG subunit was present, the highly glycosylated alpha-DG subunit was strongly reduced in surgically derived human glioblastoma biopsies, in low passage patient-derived cultures and in glioma cell lines, U87MG and A172MG, but not in all glioma cell lines tested. Immunohistochemistry of tumor frozen sections revealed that the loss of a-DG was confined in the tumor area but not around blood vessels. Overexpression of DG decreased the growth rate of the glioma cell lines lacking the highly glycosylated alpha-DG subunit and the colony-forming efficiency. Clonogenic assay in presence of temozolomide showed an additive effect between DG overexpression and drug treatment. Our data suggest that DG may be involved in the progression of primary brain tumors.