Novel therapeutic targets in the brain tumor microenvironment.
Novel therapeutic targets in the brain tumor microenvironment.
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DOI：
10.18632/oncotarget.526
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Phillips JJ
中科院分区：
文献类型：
--
作者：
Phillips JJ
胶质母细胞瘤（GBM）是成人和儿童的一种高度恶性脑肿瘤，广泛侵入非肿瘤性大脑。尽管目前的治疗干预积极，但仍非常需要改进的治疗策略。已知肿瘤与其微环境成分之间的相互作用可调节恶性肿瘤，硫酸乙酰肝素蛋白聚糖（HSPG）很重要，因为它们结合多种细胞外蛋白，包括生长因子和细胞粘附分子，调节几种配体介导的信号传导途径的活性。我们小组最近的工作描述了GBM通过细胞外微环境中硫酸乙酰肝素蛋白聚糖（HSPG）的酶促改变来调节PDGFR-α信号传导的机制。阻断肿瘤诱导的HSPG改变，这可以通过药理学策略实现，可能会抑制肿瘤细胞中的多种致癌信号通路，并破坏关键的肿瘤微环境相互作用。在这里，我们研究HSPGs和酶，修改他们在GBM。我们比较了它们在肿瘤亚型中的表达，它们在肿瘤发生中的潜在作用，以及它们作为GBM新治疗靶点的潜力。
Glioblastoma (GBM), a highly malignant brain tumor of adults and children, diffusely invades within the non-neoplastic brain. Despite aggressive current therapeutic interventions, improved therapeutic strategies are greatly needed. Interactions between the tumor and constituents of its microenvironment are known to regulate malignancy, and heparan sulfate proteoglycans (HSPGs) are important as they bind diverse extracellular proteins, including growth factors and cell adhesion molecules, regulating the activity of several ligand-mediated signaling pathways. Recent work from our group described a mechanism by which GBM regulates PDGFR-alpha signaling via enzymatic alteration of heparan sulfate proteoglycans (HSPGs) in the extracellular microenvironment. Blocking tumor-induced alterations of HSPGs, which can be achieved by pharmacological strategies, would potentially inhibit multiple oncogenic signaling pathways in tumor cells and disrupt critical tumor-microenvironment interactions. Here we examine HSPGs and the enzymes that modify them in GBM. We compare their expression across tumor subtypes, their potential roles in oncogenesis, and their potential as novel therapeutic targets in GBM.
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