STRUCTURE AND ROLE OF A TRANSFORMATION-SENSITIVE CELL SURFACE GLYCOPROTEIN

纤维连接蛋白和其他细胞外分子在细胞内起着至关重要的作用 粘附、迁移和侵袭。多肽识别序列 细胞与纤连蛋白和其他蛋白质相互作用所必需的是 其特征在于合成肽分析和定点 诱变各种合成肽抑制剂从纤连蛋白， 层粘连蛋白和胶原蛋白作为迁移抑制剂进行了比较， 几种人类肿瘤细胞。含有Arg-Gly-Asp的肽 序列是最有效的。抗整联蛋白抗体是 特别有效的抑制剂。抗α 5和抗α 2单克隆抗体 抗体显示特异性，这取决于所用的配体。 迁移基质，即分别用于纤连蛋白和胶原蛋白。一个 抗β_1单克隆抗体是各种肿瘤最普遍的抑制剂， 底物，以及抑制肿瘤细胞的侵袭， 浓度的正在完成一种细胞类型的合作研究， 黑色素瘤和一些淋巴细胞所使用的特异性粘附位点。最小 关键序列似乎是Leu-Asp-瓦尔;该序列也存在于 其他粘附蛋白。一种新的热休克蛋白， 恶性转化后减少，发现特异性结合 胎球蛋白以及胶原蛋白，表明比 以前知道的。研究将继续对其他关键多肽 序列，它们在粘附、迁移和侵袭中的作用，以及 开发新的功能抑制剂。

Fibronectin and other extracellular molecules play crucial roles in cell adhesion, migration, and invasion. Polypeptide recognition sequences necessary for cell interactions with fibronectin and other proteins are being characterized by synthetic peptide analyses and site-directed mutagenesis. A variety of synthetic peptide inhibitors from fibronectin, laminin, and collagen were compared as inhibitors of the migration of several types of human tumor cells. Peptides containing the Arg-Gly-Asp sequence were the most effective. Anti-integrin antibodies were particularly effective inhibitors. Anti-alpha5 and anti-alpha2 monoclonal antibodies displayed specificity depending on the ligand used for the migration substrate, i.e. for fibronectin and collagen, respectively. An anti-beta1 monoclonal antibody was the most general inhibitor on various substrates, as well as inhibiting tumor cell invasion at microgram concentrations. Collaborative studies are being completed on a cell-type specific adhesion site used by melanomas and some lymphocytes. The minimal critical sequence appears to be Leu-Asp-Val; this sequence is also present in other adhesion proteins. A novel heat-shock protein previously shown to be decreased after malignant transformation was found to bind specifically to fetuin as well as to collagen, indicating a broader function than previously known. Studies will continue on other crucial polypeptide sequences, on their roles in adhesion, migration, and invasion, and on developing novel inhibitors of their functions.