Zheng Peng-Sheng, Wen Jianping, Ang Lee Cyn, Sheng Wang, Viloria-Petit Alicia, Wang Yelina, Wu Yaojiong, Kerbel Robert S, Yang Burton B
Sunnybrook & Women's College Health Sciences Centre, Toronto, Canada.
FASEB J. 2004 Apr;18(6):754-6. doi: 10.1096/fj.03-0545fje. Epub 2004 Feb 6.
Versican/PG-M is an extracellular matrix proteoglycan, expression of which is elevated in a variety of human tumors. The significance of this change is unclear. Here we show that versican G3-containing fragments are present at high levels in human astrocytoma. Expression of a versican G3 construct in U87 astrocytoma cells enhances colony growth in soft agarose gel and tumor growth and blood vessel formation in nude mice. The G3-containing medium enhances endothelial cell adhesion, proliferation, and migration. G3-expressing cells and tumors formed by these cells express increased levels of fibronectin and vascular endothelial growth factor (VEGF). Furthermore, the G3 domain directly binds to fibronectin and forms a complex together with VEGF. In the presence of these three molecules, endothelial cell adhesion, proliferation, and migration were found to be significantly enhanced. Removal of the complex containing these molecules reverses these processes. Taken together, these findings implicate G3 as a modifier of tumor growth and angiogenesis and suggest a new avenue for development of anticancer and anti-angiogenic therapies based on targeting versican G3 fragments.
多功能蛋白聚糖/PG-M是一种细胞外基质蛋白聚糖，其在多种人类肿瘤中的表达升高。这种变化的意义尚不清楚。在此我们表明，含多功能蛋白聚糖G3的片段在人类星形细胞瘤中高水平存在。在U87星形细胞瘤细胞中表达多功能蛋白聚糖G3构建体可增强其在软琼脂糖凝胶中的集落生长以及在裸鼠中的肿瘤生长和血管形成。含G3的培养基可增强内皮细胞的黏附、增殖和迁移。表达G3的细胞以及由这些细胞形成的肿瘤中纤连蛋白和血管内皮生长因子（VEGF）的表达水平升高。此外，G3结构域直接与纤连蛋白结合，并与VEGF形成复合物。在这三种分子存在的情况下，发现内皮细胞的黏附、增殖和迁移显著增强。去除含有这些分子的复合物可逆转这些过程。综上所述，这些发现表明G3是肿瘤生长和血管生成的调节因子，并为基于靶向多功能蛋白聚糖G3片段开发抗癌和抗血管生成疗法提供了一条新途径。
