Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, India.
Proteomics Laboratory, National Centre for Cell Science, Ganeshkhind, Pune, India.
Sci Rep. 2017 May 3;7(1):1449. doi: 10.1038/s41598-017-01202-8.
Glioblastoma multiforme (GBM), the most malignant of all gliomas is characterized by a high degree of heterogeneity and poor response to treatment. The sub-ventricular zone (SVZ) is the major site of neurogenesis in the brain and is rich in neural stem cells. Based on the proximity of the GBM tumors to the SVZ, the tumors can be further classified into SVZ+ and SVZ-. The tumors located in close contact with the SVZ are classified as SVZ+, while the tumors located distantly from the SVZ are classified as SVZ-. To gain an insight into the increased aggressiveness of SVZ+ over SVZ- tumors, we have used proteomics techniques like 2D-DIGE and LC-MS/MS to investigate any possible proteomic differences between the two subtypes. Serum proteomic analysis revealed significant alterations of various acute phase proteins and lipid carrying proteins, while tissue proteomic analysis revealed significant alterations in cytoskeletal, lipid binding, chaperone and cell cycle regulating proteins, which are already known to be associated with disease pathobiology. These findings provide cues to molecular basis behind increased aggressiveness of SVZ+ GBM tumors over SVZ- GBM tumors and plausible therapeutic targets to improve treatment modalities for these highly invasive tumors.
多形性胶质母细胞瘤（GBM）是所有神经胶质瘤中恶性程度最高的，其特征是高度异质性和对治疗反应不佳。脑室下区（SVZ）是大脑中神经发生的主要部位，富含神经干细胞。根据 GBM 肿瘤与 SVZ 的接近程度，肿瘤可以进一步分为 SVZ+和 SVZ-。与 SVZ 密切接触的肿瘤被归类为 SVZ+，而远离 SVZ 的肿瘤被归类为 SVZ-。为了深入了解 SVZ+肿瘤比 SVZ-肿瘤更具侵袭性，我们使用 2D-DIGE 和 LC-MS/MS 等蛋白质组学技术来研究这两种亚型之间是否存在任何可能的蛋白质组差异。血清蛋白质组分析显示各种急性期蛋白和脂质携带蛋白发生了显著改变，而组织蛋白质组分析显示细胞骨架、脂质结合、伴侣和细胞周期调节蛋白发生了显著改变，这些蛋白已经与疾病的病理生物学有关。这些发现为 SVZ+GBM 肿瘤比 SVZ-GBM 肿瘤侵袭性增加的分子基础提供了线索，并为改善这些高度侵袭性肿瘤的治疗方法提供了合理的治疗靶点。
