The high affinity heparin-binding domain and the V region of fibronectin mediate invasion of human oral squamous cell carcinoma cells in vitro
The high affinity heparin-binding domain and the V region of fibronectin mediate invasion of human oral squamous cell carcinoma cells in vitro
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DOI：
10.1074/jbc.272.30.18932
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发表时间：
1997-07-25
影响因子：
4.8
通讯作者：
Johnson, PW
中科院分区：
文献类型：
--
作者：
Kapila, YL;Niu, JJ;Johnson, PW
纤连蛋白是一种细胞外基质分子，由可形成功能域的重复亚基组成。这些结构域包含肝素和调节细胞功能的各种细胞表面受体的多个结合位点。为了研究高亲和力肝素结合区和纤连蛋白可变剪接 V 区在肿瘤侵袭中的作用，我们表达并纯化了四种互补的重组纤连蛋白。这些蛋白质包含或排除可变剪接的 V 区，并含有突变的非功能性高亲和力肝素结合结构域 (Hep(-)) 或未突变的肝素结合结构域 (Hep(+))。 检测培养的口腔鳞状细胞癌细胞对补充有这四种纯化重组蛋白的基质胶/胶原基质的侵袭，以及在塑料上的铺展和运动。 V(-)Hep(+) 蛋白与 V(-)Hep(-) 蛋白相比。蛋白质中包含V区增强了与Hep(+)和Hep(-)蛋白相关的侵袭和迁移，而Hep(+)重组蛋白增强了细胞扩散。这些数据表明，高亲和力肝素结合结构域和纤连蛋白的V区在口腔鳞状细胞癌细胞的侵袭、运动和扩散中发挥重要作用。
Fibronectin is an extracellular matrix molecule composed of repeating subunits that create functional domains. These domains contain multiple binding sites for heparin and for various cell-surface receptors that modulate cell function. To examine the role that the high affinity heparin-binding region and the alternatively spliced V region of fibronectin play in tumor invasion, we expressed and purified four complementary recombinant fibronectin proteins. These proteins either included or excluded the alternatively spliced V region and contained either a mutated, non-functional high affinity heparin-binding domain (Hep(-)) or an unmutated heparin-binding domain (Hep(+)), Cultured oral squamous cell carcinoma cells were assayed for invasion into a Matrigel/collagen matrix supplemented with these four purified recombinant proteins, and for spreading and motility on plastic, Increased invasion was observed in gels supplemented with the V(-)Hep(+) protein when compared with the V(-)Hep(-) protein. Inclusion of the V region in the proteins enhanced the invasion and migration associated with both Hep(+) and Hep(-) proteins, whereas cell spreading was enhanced with the Hep(+) recombinant proteins, These data demonstrate that both the high affinity heparin-binding domain and the V region of fibronectin play important roles in invasion, motility, and spreading of oral squamous cell carcinoma cells.