Sunnybrook Research Institute, Sunnybrook Health Sciences Centre and Centre for the Study of Bone Metastasis, Odette Cancer Centre, Toronto, Ontario, Canada.
FEBS Lett. 2013 Jan 16;587(2):185-92. doi: 10.1016/j.febslet.2012.11.023. Epub 2012 Nov 28.
Versican is a proteoglycan expressed in the extracellular matrix, where it regulates a variety of cell activities and affects tumor development. With alternative splicing, there are four versican isoforms, denoted V0, V1, V2 and V3. The V2 isoform is highly expressed in the mature brain but its function in the mature brain has not yet been elucidated. Since brain tumors are among the most angiogenic of human tumors, we investigated whether or not the V2 isoform plays a role in angiogenesis and found that the glioblastoma cell line U87 stably transfected with V2 formed tumors containing extensive vasculature. Although the V2-expressing cells grew slowly, they survived well in serum-free medium. They also displayed high adhesive ability to endothelial cells and facilitated tube-like structure formation. Importantly, fibronectin was up-regulated by V2 and mediated V2 function. Thus, versican V2 could be a potential target for intervention of brain tumor angiogenesis.
神经节苷脂是一种在细胞外基质中表达的蛋白聚糖，它调节多种细胞活动，并影响肿瘤的发展。通过选择性剪接，有四种神经节苷脂异构体，分别表示为 V0、V1、V2 和 V3。V2 异构体在成熟的大脑中高度表达，但它在成熟的大脑中的功能尚未阐明。由于脑肿瘤是人类肿瘤中血管生成最活跃的肿瘤之一，我们研究了 V2 异构体是否在血管生成中发挥作用，发现稳定转染 V2 的神经胶质瘤细胞系 U87 形成了含有广泛血管的肿瘤。虽然表达 V2 的细胞生长缓慢，但它们在无血清培养基中存活良好。它们还表现出对内皮细胞的高黏附能力，并促进管状结构的形成。重要的是，V2 上调了纤维连接蛋白并介导了 V2 的功能。因此，神经节苷脂 V2 可能是干预脑肿瘤血管生成的潜在靶点。
