BIOLOGICAL MODULATION OF HUMAN MELANOMA CELL INVASION

人类黑色素瘤细胞侵袭的生物调节

• 批准号: 3183871
• 负责人: MARY J.C. HENDRIX
• 金额: $ 11.17万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183871
• 关键词: amnion; antifibrinolytic agents; basement membrane; cancer registry /resource; electron microscopy; fibrinolytic agents; gel electrophoresis; human tissue; immunochemistry; membrane activity; metastasis; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer invasiveness; neoplastic cell; plasminogen activator; radiotracer; tumor antigens

Metastatic melanoma has rapidly increased in incidence throughout the world during the past decade. This insidious disease is generally undetected by many patients until reaching incurable stages. Since metastatic melanoma is currently considered to be incurable, research scientists have been encouraged to explore new avenues of cancer treatment which may provide hopeful perspectives in the handling of this invasive disease. Studies aimed at understanding the biological progression of this invasive process would undoubtedly be useful. The overall objective of our proposed research is to further explore, in a reliable in vitro model which we have developed, the study of human melanoma cell invasion that has been shown to correlate with an in vivo animal model; specifically, the heterogeneous invasive characteristics of high and low metastatic variants of melanoma cells as they interact with an extracellular basement membrane (human amnion) in the absence and presence of possible inhibitors and enhancers. The specific aims for this three-year project are: (1) to examine the intracellular and cell surface associated interactions of preinvasive, invasive and postinvasive melanoma tumor cells interacting with basement membranes in vitro; (2) to study the mechanism of tumor cell degradation by identifying the specific type(s) of plasminogen activator (PA) and/or proactivators and the physiological inhibitors of these activators produced by high and low metastatic variants in the invasion model; also, to measure the amount of PA activity associated with the cells when placed onto membranes; (3) to study the magnitude of the inhibitory or stimulatory effects of a specific biological response modifier, the exogenous addition of fibrinolytic components or antibodies to these components on melanoma tumor cells in vitro (particularly their degradative ability) as they interact with an extracellular barrier; and (4) to explore the nature of certain cell surface components that participate in tumor invasion. The latter will include the use of monoclonal antibodies to highly metastatic cell surface antigens (cell membrane glycoconjugates) of highly metastatic cells which could possibly modulate tumor cell invasion.

转移性黑色素瘤在世界范围内的发病率迅速增加 在过去的十年里。 这种隐匿的疾病一般不会被发现 许多患者直到达到无法治愈的阶段。 由于转移性黑色素瘤 目前被认为是无法治愈的，研究科学家们已经 鼓励探索癌症治疗的新途径，这可能会提供 处理这种侵袭性疾病的充满希望的前景。 研究 旨在了解这种侵入过程的生物学进展 无疑是有用的。 我们提议的总体目标 研究是在我们拥有的可靠的体外模型中进一步探索 对人类黑色素瘤细胞侵袭的研究已被证明 与体内动物模型相关；具体来说，异质 黑色素瘤高转移变异和低转移变异的侵袭特征 细胞与细胞外基底膜（人类 羊膜）在存在或不存在可能的抑制剂和增强剂的情况下。 这个为期三年的项目的具体目标是：（1）审查 细胞内和细胞表面相关的侵袭前相互作用， 侵袭性和侵袭后黑色素瘤肿瘤细胞与基底相互作用 体外膜； (2)研究肿瘤细胞降解机制 识别纤溶酶原激活剂 (PA) 的具体类型和/或 产生的前激活剂和这些激活剂的生理抑制剂 通过侵袭模型中的高转移变异和低转移变异；还可以测量 当放置在细胞上时与细胞相关的 PA 活性量 膜； (3) 研究抑制或刺激的幅度 特定生物反应调节剂的影响，外源添加 黑色素瘤上的纤溶成分或这些成分的抗体 体外肿瘤细胞（特别是它们的降​​解能力），因为它们 与细胞外屏障相互作用； (4) 探索本质 某些参与肿瘤侵袭的细胞表面成分。 这 后者将包括使用单克隆抗体来治疗高度转移的 高度转移的细胞表面抗原（细胞膜糖缀合物） 可能调节肿瘤细胞侵袭的细胞。