Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Adv Exp Med Biol. 2020;1245:147-161. doi: 10.1007/978-3-030-40146-7_7.
The biology of tumor cells strictly depends on their microenvironment architecture and composition, which controls the availability of growth factors and signaling molecules. Thus, the network of glycosaminoglycans, proteoglycans, and proteins known as extracellular matrix (ECM) that surrounds the cells plays a central role in the regulation of tumor fate. Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPGs) are highly versatile ECM components that bind and regulate the activity of growth factors, cell membrane receptors, and other ECM molecules. These HS binding partners modulate cell adhesion, motility, and proliferation that are processes altered during tumor progression. Modification in the expression and activity of HS, HSPGs, and the respective metabolic enzymes results unavoidably in alteration of tumor cell microenvironment. In this light, the targeting of HS structure and metabolism is potentially a new tool in the treatment of different cancer types.
肿瘤细胞的生物学特性严格依赖于其微环境的结构和组成，而微环境的结构和组成又控制着生长因子和信号分子的可利用性。因此，细胞周围的糖胺聚糖、蛋白聚糖和被称为细胞外基质（ECM）的蛋白质网络在调节肿瘤命运方面起着核心作用。硫酸乙酰肝素（HS）和硫酸乙酰肝素蛋白聚糖（HSPGs）是高度多样化的 ECM 成分，它们可以结合并调节生长因子、细胞膜受体和其他 ECM 分子的活性。这些与 HS 结合的配体调节细胞黏附、运动和增殖，这些过程在肿瘤进展过程中会发生改变。HS、HSPGs 及其各自代谢酶的表达和活性的改变不可避免地会导致肿瘤细胞微环境的改变。从这个角度来看，靶向 HS 结构和代谢可能是治疗不同癌症类型的一种新工具。
