Sottile J, Hocking D C, Swiatek P J
Department of Physiology and Cell Biology (A-134), Neil Hellman Medical Research Building, Albany Medical College, Albany, NY 12208, USA.
J Cell Sci. 1998 Oct;111 ( Pt 19):2933-43. doi: 10.1242/jcs.111.19.2933.
Cell growth control in non-transformed cells depends, in part, on adhesive interactions with the extracellular matrix. Following injury, excess or altered fibronectin deposition into the extracellular matrix may contribute to the pathogenesis of fibrosis and atherosclerosis by triggering changes in specific cell functions associated with wound repair, including cell proliferation and migration. To assess the role of fibronectin polymerization on cell growth, we isolated mouse embryonic cells that lack endogenous fibronectin (fibronectin-null cells) and established them in culture under serum-free conditions. These fibronectin-null cells do not produce any detectable fibronectin, but are capable of assembling a fibronectin matrix when cultured in the presence of exogenously added fibronectin. Our data indicate that adhesion-dependent growth in fibronectin-null cells is dramatically increased (>2-5x) by culturing cells in the presence of fibronectin. This fibronectin-induced cell growth was blocked by inhibiting fibronectin matrix assembly. Arg-Gly-Asp peptides or fragments of fibronectin that contain the Arg-Gly-Asp cell binding site promoted clustering of the (&agr ;)5beta1 integrin in focal adhesions, but did not enhance cell growth. These data indicate that the polymerization of fibronectin into the extracellular matrix positively regulates cell growth, and that occupancy and clustering of fibronectin-binding integrins alone are not sufficient to trigger increased cell growth.
未转化细胞中的细胞生长控制部分取决于与细胞外基质的黏附相互作用。损伤后，纤连蛋白在细胞外基质中过量沉积或沉积改变，可能通过触发与伤口修复相关的特定细胞功能变化，包括细胞增殖和迁移，从而促进纤维化和动脉粥样硬化的发病机制。为了评估纤连蛋白聚合对细胞生长的作用，我们分离了缺乏内源性纤连蛋白的小鼠胚胎细胞（纤连蛋白缺失细胞），并在无血清条件下进行培养。这些纤连蛋白缺失细胞不产生任何可检测到的纤连蛋白，但在添加外源性纤连蛋白的情况下培养时，能够组装纤连蛋白基质。我们的数据表明，在纤连蛋白存在的情况下培养细胞，纤连蛋白缺失细胞中依赖黏附的生长显著增加（>2 - 5倍）。这种纤连蛋白诱导的细胞生长通过抑制纤连蛋白基质组装而被阻断。含有精氨酸 - 甘氨酸 - 天冬氨酸（Arg - Gly - Asp）细胞结合位点的Arg - Gly - Asp肽或纤连蛋白片段促进了粘着斑中（α）5β1整合素的聚集，但并未增强细胞生长。这些数据表明，纤连蛋白聚合成细胞外基质对细胞生长具有正向调节作用，并且仅纤连蛋白结合整合素的占据和聚集不足以触发细胞生长增加。
