Wade Anna, Engler Jane R, Tran Vy M, Phillips Joanna J
Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA, USA.
Methods Mol Biol. 2015;1229:507-16. doi: 10.1007/978-1-4939-1714-3_39.
Extracellular sulfatases (SULF1 and SULF2) selectively remove 6-O-sulfate groups from heparan sulfate proteoglycans (HSPGs) and by this process control important interactions of HSPGs with extracellular factors including morphogens, growth factors, and extracellular matrix 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 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）可选择性地从硫酸乙酰肝素蛋白聚糖（HSPG）中去除6-O-硫酸基团，并通过这一过程控制HSPG与包括形态发生素、生长因子和细胞外基质成分在内的细胞外因子的重要相互作用。SULF1和SULF2的表达在发育过程中受到动态调节，在诸如胶质母细胞瘤（GBM）等病理状态下会发生改变，GBM是一种高度恶性和高侵袭性的脑癌。SULF2蛋白在人类GBM的一个重要亚组中增加，并且在该疾病的小鼠模型中有助于调节受体酪氨酸激酶信号传导和肿瘤生长。通过改变配体与HSPG的结合，SULF2有可能改变在包括增殖、趋化性和迁移在内的许多细胞过程中起重要作用的因子的细胞外可用性。恶性肿瘤细胞向周围健康脑组织的弥漫性侵袭是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侵袭联系起来。
