Department of Neurological Surgery, UCSF, San Francisco, CA 94158, USA.
FEBS J. 2013 May;280(10):2399-417. doi: 10.1111/febs.12109. Epub 2013 Feb 6.
Glioblastoma, a malignant brain cancer, is characterized by abnormal activation of receptor tyrosine kinase signalling pathways and a poor prognosis. Extracellular proteoglycans, including heparan sulfate and chondroitin sulfate, play critical roles in the regulation of cell signalling and migration via interactions with extracellular ligands, growth factor receptors and extracellular matrix components, as well as intracellular enzymes and structural proteins. In cancer, proteoglycans help drive multiple oncogenic pathways in tumour cells and promote critical tumour-microenvironment interactions. In the present review, we summarize the evidence for proteoglycan function in gliomagenesis and examine the expression of proteoglycans and their modifying enzymes in human glioblastoma using data obtained from The Cancer Genome Atlas (http://cancergenome.nih.gov/). Furthermore, we demonstrate an association between specific proteoglycan alterations and changes in receptor tyrosine kinases. Based on these data, we propose a model in which proteoglycans and their modifying enzymes promote receptor tyrosine kinase signalling and progression in glioblastoma, and we suggest that cancer-associated proteoglycans are promising biomarkers for disease and therapeutic targets.
胶质母细胞瘤是一种恶性脑癌，其特征是受体酪氨酸激酶信号通路异常激活和预后不良。细胞外蛋白聚糖，包括肝素硫酸盐和软骨素硫酸盐，通过与细胞外配体、生长因子受体和细胞外基质成分以及细胞内酶和结构蛋白相互作用，在细胞信号转导和迁移的调节中发挥关键作用。在癌症中，蛋白聚糖有助于驱动肿瘤细胞中的多个致癌途径，并促进关键的肿瘤微环境相互作用。在本综述中，我们总结了蛋白聚糖在神经胶质瘤发生中的功能证据，并使用从癌症基因组图谱（http://cancergenome.nih.gov/）获得的数据，检查了人胶质母细胞瘤中蛋白聚糖及其修饰酶的表达。此外，我们证明了特定蛋白聚糖改变与受体酪氨酸激酶变化之间存在关联。基于这些数据，我们提出了一个模型，其中蛋白聚糖及其修饰酶促进胶质母细胞瘤中受体酪氨酸激酶信号转导和进展，并且我们认为与癌症相关的蛋白聚糖是疾病和治疗靶标的有前途的生物标志物。
