Department of Neurological Surgery, Brain Tumor Research Center, Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Methods Mol Biol. 2022;2303:415-425. doi: 10.1007/978-1-0716-1398-6_33.
Extracellular sulfatases (SULF1 and SULF2) selectively remove 6-O-sulfate groups (6OS) from heparan sulfate proteoglycans (HSPGs) and by this process control important interactions of HSPGs with extracellular factors including morphogens, growth factors, and extracellular matrix (ECM) components. The expression of SULF1 and SULF2 is dynamically regulated during development and is altered in pathological states such as glioblastoma (GBM), a highly malignant and highly invasive brain cancer. SULF2 protein is increased in an important subset of human GBM and it helps regulate receptor tyrosine kinase (RTK) signaling and tumor growth in a murine model of the disease. By altering ligand binding to HSPGs SULF2 has the potential to modify the extracellular availability of factors important in a number of cell processes including proliferation, chemotaxis, and migration. Diffuse invasion of malignant tumor cells into surrounding healthy brain is a characteristic feature of GBM that makes therapy challenging. Here, we describe methods to assess SULF2 expression in human tumor tissue and cell lines and how to relate this to tumor cell invasion.
细胞外硫酸酯酶（SULF1 和 SULF2）选择性地从硫酸乙酰肝素蛋白聚糖（HSPGs）上去除 6-O-硫酸基团（6OS），通过这种过程控制 HSPGs 与包括形态发生素、生长因子和细胞外基质（ECM）成分等细胞外因子的重要相互作用。SULF1 和 SULF2 的表达在发育过程中是动态调节的，并且在病理状态下如神经胶质瘤（GBM）中发生改变，GBM 是一种高度恶性和高度侵袭性的脑癌。SULF2 蛋白在人类 GBM 的一个重要亚群中增加，并有助于调节疾病的小鼠模型中的受体酪氨酸激酶（RTK）信号和肿瘤生长。通过改变配体与 HSPGs 的结合，SULF2 有可能改变包括增殖、趋化性和迁移在内的许多细胞过程中重要因子的细胞外可用性。恶性肿瘤细胞向周围健康大脑的弥漫性浸润是 GBM 的一个特征，这使得治疗具有挑战性。在这里，我们描述了评估人类肿瘤组织和细胞系中 SULF2 表达的方法，以及如何将其与肿瘤细胞浸润相关联。
