Jiang Xinnong, Couchman John R
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Histochem Cytochem. 2003 Nov;51(11):1393-410. doi: 10.1177/002215540305101101.
Perlecan is a major heparan sulfate proteoglycan (HSPG) of basement membranes (BMs) and connective tissues. The core protein of perlecan is divided into five domains based on sequence homology to other known proteins. Commonly, the N-terminal domain I of mammalian perlecan is substituted with three HS chains that can bind a number of matrix molecules, cytokines, and growth factors. Perlecan is essential for metazoan life, as shown by genetic manipulations of nematodes, insects, and mice. There are also known human mutations that can be lethal. In vertebrates, new functions of perlecan emerged with the acquisition of a closed vascular system and skeletal connective tissues. Many of perlecan's functions may be related to the binding and presentation of growth factors to high-affinity tyrosine kinase (TK) receptors. Data are accumulating, as discussed here, that similar growth factor-mediated processes may have unwanted promoting effects on tumor cell proliferation and tumor angiogenesis. Understanding of these attributes at the molecular level may offer opportunities for therapeutic intervention.
基底膜聚糖是基底膜（BMs）和结缔组织中的一种主要硫酸乙酰肝素蛋白聚糖（HSPG）。根据与其他已知蛋白质的序列同源性，基底膜聚糖的核心蛋白可分为五个结构域。通常，哺乳动物基底膜聚糖的N端结构域I被三条硫酸乙酰肝素链取代，这些链可结合多种基质分子、细胞因子和生长因子。如对线虫、昆虫和小鼠的基因操作所示，基底膜聚糖对后生动物的生命至关重要。也有已知的可致死的人类突变。在脊椎动物中，随着封闭血管系统和骨骼结缔组织的获得，基底膜聚糖出现了新功能。基底膜聚糖的许多功能可能与生长因子与高亲和力酪氨酸激酶（TK）受体的结合和呈递有关。如下文所讨论的，越来越多的数据表明，类似的生长因子介导的过程可能对肿瘤细胞增殖和肿瘤血管生成产生不良促进作用。在分子水平上了解这些特性可能为治疗干预提供机会。
