Inserm U837, Bâtiment Biserte, Place de Verdun, 59045 Lille Cedex, France.
J Neuropathol Exp Neurol. 2010 Jun;69(6):606-22. doi: 10.1097/NEN.0b013e3181e00579.
Glioblastomas are the most common primary central nervous system tumors in adults, and they remain resistant to current treatments. erbB1 signaling is frequently altered in glioblastomas, suggesting thaterbB receptor family members may represent targets for molecular therapy. We performed a comprehensive analysis of erbB receptor and ligand expression profiles in a panel of 9 glioblastomas andcompared them to nonneoplastic cerebral tissue containing neocortex and adjacent white matter. Quantitative reverse transcription-polymerase chain reaction and Western blot analysis showed that erbB1signaling and erbB2 receptors exhibited highly variable deregulation profiles in the tumors, with patterns ranging from underexpression to overexpression; in contrast, erbB3 and erbB4 were downregulated. We next performed immunohistochemistry to determinethe distribution patterns of erbB receptors among the main neuralcell types in the tumors with special reference to the putative tumor stem cell population. Results revealed intertumoral and intratumoral heterogeneity in all 4 erbB expression profiles, but each receptor exhibited a distinct distribution pattern among glial fibrillary acidic protein-, Olig2-, NeuN-, and CD133-positive populations. Although erbB1 immunoreactivity was detected in only small subsets of CD133-positive putative tumor stem cells, erbB3 immunoreactivity was prominent in this population, suggesting that erbB3 may represent a new potential therapeutic target.
胶质母细胞瘤是成人中枢神经系统最常见的原发性肿瘤，目前的治疗方法对此仍然无效。erbB1 信号在胶质母细胞瘤中经常发生改变，这表明 erbB 受体家族成员可能是分子治疗的靶点。我们对一组 9 例胶质母细胞瘤中的 erbB 受体和配体表达谱进行了全面分析，并将其与包含新皮质和相邻白质的非肿瘤性脑组织进行了比较。定量逆转录聚合酶链反应和 Western blot 分析显示，erbB1 信号和 erbB2 受体在肿瘤中表现出高度可变的失调谱，从表达下调到表达上调不等；相比之下，erbB3 和 erbB4 则下调。接下来，我们进行了免疫组织化学分析，以确定 erbB 受体在肿瘤中主要神经细胞类型中的分布模式，特别关注可能的肿瘤干细胞群体。结果显示，所有 4 种 erbB 表达谱在肿瘤内和肿瘤间均存在异质性，但每种受体在胶质纤维酸性蛋白阳性、Olig2 阳性、NeuN 阳性和 CD133 阳性群体中均表现出不同的分布模式。虽然 erbB1 免疫反应仅在一小部分 CD133 阳性的肿瘤干细胞中检测到，但 erbB3 免疫反应在该群体中较为明显，提示 erbB3 可能代表一个新的潜在治疗靶点。
