CELL ADHESION IN NEOPLASIA AFFECTING HUMAN COMMUNICATION

工作总结： 本项目的目的是阐明 细胞的粘附和识别是细胞生长和迁移所必需的。 上皮鳞状细胞肿瘤中的肿瘤细胞和支持细胞 呼吸消化道，以便开发药理学和 分子预防和治疗。 整合素细胞粘附分子的一个库， 鳞状细胞癌和形成血管的内皮细胞 血管血液供应的特征在于免疫生物化学和 免疫组织化学方法。 特异性抗体和 这些整联蛋白受体的小分子受体拮抗剂， 在体外抑制肿瘤和内皮细胞附着和生长， 在体内已经是正在进行的研究的主题。 附接 层粘连蛋白，细胞外基质产生的肿瘤细胞， 肿瘤，被证明主要是由于三个整合素受体 在体外使用特异性抗体。 研究评估这些 受体在肿瘤发展中起重要作用， 治疗靶点有待小分子抑制剂的开发 每一个受体。 在使用内皮整合素受体拮抗剂的研究中， 整联蛋白受体家族似乎在生长中很重要， 在肿瘤诱导的新血管生成过程中内皮细胞的迁移。在 初步实验中，内皮整合素受体拮抗剂， 发现其在体内抑制鳞状细胞癌的生长。 进一步 需要进行研究以确定最佳配方、剂量和途径 以及在临床试验中使用之前的毒性。

Summary of Work: The purpose of this project is to elucidate the molecular mechanisms of cell adhesion and recognition necessary for growth and migration of neoplastic and supporting cells in squamous cell neoplasms of the upper aerodigestive tract in order to develop approaches for pharmacologic and molecular prevention and therapy. A repertoire of integrin cell adhesion molecules that are overexpressed by squamous cell carcinomas and by the endothelial cells that form the vascular blood supply has been characterized by immunobiochemical and immunohistochemical methods. The ability of specific antibodies and small molecule receptor antagonists of these integrin receptors to inhibit attachment and growth of tumor and endothelial cells in vitro and in vivo have been the subject of ongoing investigations. The attachment of tumor cells to laminin, the extracellular matrix produced by the tumors, was shown to be predominantly due to three integrin receptors using specific antibodies in vitro. Studies to evaluate whether these receptors play an important role in tumor development and may be suitable targets for therapy await the development of small molecule inhibitors to each of these receptors. In studies using endothelial integrin receptor antagonists, members of the integrin receptor family appear to be important in the growth and migration of endothelial cells during tumor induced neoangiogenesis. In preliminary experiments, endothelial integrin receptor antagonists were found to inhibit the growth of squamous cell carcinomas in vivo. Further studies will be needed to determine optimal formulation, dose and route as well as toxicity before use in clinical trials may be undertaken.