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CELL ADHESION IN NEOPLASIA AFFECTING HUMAN COMMUNICATION

影响人类交流的肿瘤细胞粘附

基本信息

批准号：
6104218
负责人：
CARTER VAN WAES
金额：
--
依托单位：
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

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 has 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 the past year, endothelial integrin receptor antagonists were identified which inhibit the growth of squamous cell carcinomas in vivo. The inhibitors were shown to directly inhibit proliferation of endothelial but not tumor cells in vitro, consistent with a primary effect upon angiogenesis.

这个项目的目的是阐明细胞粘附和识别的分子机制肿瘤细胞和支持细胞的生长和迁移上呼吸消化道鳞状细胞肿瘤开发药理学和分子预防方法，和心理治疗一种整联蛋白细胞粘附分子库，在鳞状细胞癌中过度表达，形成血管血液供应的内皮细胞已经被通过免疫生物化学和免疫组织化学方法.特异性抗体和小分子这些整联蛋白受体的受体拮抗剂，肿瘤细胞与内皮细胞在体外和体内的粘附和生长体内一直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体外使用特定抗体的受体。研究来评价这些受体是否在肿瘤中起重要作用开发和可能是合适的治疗靶点等待开发针对这些受体的小分子抑制剂。在使用内皮整合素受体拮抗剂的研究中，整合素受体家族中的一个似乎在生长中起重要作用，和迁移的内皮细胞在肿瘤诱导新血管生成在过去的一年里，内皮整合素受体确定了抑制鳞状上皮细胞生长的拮抗剂，体内的细胞癌。抑制剂被证明直接在体外抑制内皮细胞而非肿瘤细胞增殖，与对血管生成的主要作用一致。