Elgundi Zehra, Papanicolaou Michael, Major Gretel, Cox Thomas R, Melrose James, Whitelock John M, Farrugia Brooke L
Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW, Australia.
The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, UNSW Sydney, Darlinghurst, NSW, Australia.
Front Oncol. 2020 Jan 17;9:1482. doi: 10.3389/fonc.2019.01482. eCollection 2019.
Cancer metastasis is the dissemination of tumor cells to new sites, resulting in the formation of secondary tumors. This process is complex and is spatially and temporally regulated by intrinsic and extrinsic factors. One important extrinsic factor is the extracellular matrix, the non-cellular component of tissues. Heparan sulfate proteoglycans (HSPGs) are constituents of the extracellular matrix, and through their heparan sulfate chains and protein core, modulate multiple events that occur during the metastatic cascade. This review will provide an overview of the role of the extracellular matrix in the events that occur during cancer metastasis, primarily focusing on perlecan. Perlecan, a basement membrane HSPG is a key component of the vascular extracellular matrix and is commonly associated with events that occur during the metastatic cascade. Its contradictory role in these events will be discussed and we will highlight the recent advances in cancer therapies that target HSPGs and their modifying enzymes.
癌症转移是肿瘤细胞扩散至新的部位，从而导致继发性肿瘤的形成。这一过程十分复杂，受到内在和外在因素在空间和时间上的调控。一个重要的外在因素是细胞外基质，即组织的非细胞成分。硫酸乙酰肝素蛋白聚糖（HSPGs）是细胞外基质的组成部分，通过其硫酸乙酰肝素链和蛋白核心，调节转移级联过程中发生的多个事件。本综述将概述细胞外基质在癌症转移过程中所发生事件中的作用，主要聚焦于基底膜蛋白聚糖。基底膜硫酸乙酰肝素蛋白聚糖是血管细胞外基质的关键成分，通常与转移级联过程中发生的事件相关。将讨论其在这些事件中的矛盾作用，并重点介绍针对硫酸乙酰肝素蛋白聚糖及其修饰酶的癌症治疗的最新进展。
