Aguiar Claudia Beatriz Nedel Mendes de, Lobão-Soares Bruno, Alvarez-Silva Marcio, Trentin Andréa Gonçalves
Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
BMC Cell Biol. 2005 Aug 19;6:31. doi: 10.1186/1471-2121-6-31.
Adhesion to extracellular matrix (ECM) components has been implicated in the proliferative and invasive properties of tumor cells. We investigated the ability of C6 glioma cells to attach to ECM components in vitro and described the regulatory role of glycosaminoglycans (GAGs) on their adhesion to the substrate, proliferation and migration.
ECM proteins (type IV collagen, laminin and fibronectin) stimulate rat C6 glioma cell line adhesion in vitro, in a dose-dependent manner. The higher adhesion values were achieved with type IV collagen. Exogenous heparin or chondroitin sulfate impaired, in a dose-dependent manner the attachment of C6 glioma cell line to laminin and fibronectin, but not to type IV collagen. Dextran sulfate did not affect C6 adhesion to any ECM protein analyzed, indicating a specific role of GAGs in mediating glioma adhesion to laminin and fibronectin. GAGs and dextran sulfate did not induce C6 glioma detachment from any tested substrate suggesting specific effect in the initial step of cell adhesion. Furthermore, heparin and chondroitin sulfate impaired C6 cells proliferation on fibronectin, but not on type IV collagen or laminin. In contrast, both GAGs stimulate the glioma migration on laminin without effect on type IV collagen or fibronectin.
The results suggest that GAGs and proteoglycans regulate glioma cell adhesion to ECM proteins in specific manner leading to cell proliferation or cell migration, according to the ECM composition, thus modulating tumor cell properties.
肿瘤细胞与细胞外基质（ECM）成分的黏附与肿瘤细胞的增殖和侵袭特性有关。我们研究了C6胶质瘤细胞在体外与ECM成分黏附的能力，并描述了糖胺聚糖（GAGs）对其与底物黏附、增殖和迁移的调节作用。
ECM蛋白（IV型胶原、层粘连蛋白和纤连蛋白）以剂量依赖的方式刺激大鼠C6胶质瘤细胞系在体外的黏附。IV型胶原能实现更高的黏附值。外源性肝素或硫酸软骨素以剂量依赖的方式损害C6胶质瘤细胞系与层粘连蛋白和纤连蛋白的黏附，但不影响其与IV型胶原的黏附。硫酸葡聚糖不影响C6对所分析的任何ECM蛋白的黏附，表明GAGs在介导胶质瘤与层粘连蛋白和纤连蛋白黏附中具有特定作用。GAGs和硫酸葡聚糖均未诱导C6胶质瘤细胞从任何测试底物上脱离，提示在细胞黏附的初始步骤中具有特定作用。此外，肝素和硫酸软骨素损害C6细胞在纤连蛋白上的增殖，但不影响其在IV型胶原或层粘连蛋白上的增殖。相反，两种GAGs均刺激胶质瘤在层粘连蛋白上的迁移，而对IV型胶原或纤连蛋白无影响。
结果表明，GAGs和蛋白聚糖根据ECM组成以特定方式调节胶质瘤细胞与ECM蛋白的黏附，从而导致细胞增殖或细胞迁移，进而调节肿瘤细胞特性。
