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中起着至关重要的作用 黏附、迁移和入侵。多肽识别序列 细胞与纤维连接蛋白和其他蛋白质相互作用所必需的 通过合成肽分析和定点定位来表征 诱变。从纤维连接蛋白合成的各种多肽抑制剂， 比较了层粘连蛋白和胶原作为血管内皮细胞迁移的抑制物 几种类型的人类肿瘤细胞。含Arg-Gly-Asp的多肽 序列是最有效的。抗整合素抗体 特别有效的抑制剂。抗α5和抗α2单抗 抗体显示出特异性，这取决于用于 迁移底物，即纤维连接蛋白和胶原蛋白。一个 抗-β1单抗是多种疾病的最普遍的抑制因子。 底物，以及在微克范围内抑制肿瘤细胞侵袭 浓度。对一种细胞类型的合作研究正在完成 黑色素瘤和某些淋巴细胞使用的特殊黏附部位。最小的 关键序列似乎是Leu-Asp-Val；该序列也存在 在其他黏附蛋白中。先前发现的一种新的热休克蛋白 发现癌变后BE降低与特异性结合 与胎球蛋白和胶原蛋白一样，表明其功能比 之前已知的。对其他关键多肽的研究将继续进行 序列，关于它们在黏附、迁移和入侵中的作用 开发其功能的新型抑制剂。

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.