BIOLOGICAL MODULATION OF HUMAN MELANOMA CELL INVASION

转移性黑色素瘤在全世界的发病率迅速增加。 在过去的十年里。这种潜伏的疾病通常不会被 许多患者直到达到无法治愈的阶段。自从转移性黑色素瘤 目前被认为是不治之症，研究科学家已经 鼓励探索癌症治疗的新途径，以提供 治疗这种侵袭性疾病的前景充满希望。研究 旨在了解这种侵入性过程的生物学进程 无疑是有用的。我们建议的总体目标是 研究是进一步探索，在我们拥有的可靠的体外模型中 发展起来的对人类黑色素瘤细胞侵袭的研究已经表明 与体内动物模型相关；具体地说，异质性 黑色素瘤高、低转移变异体的侵袭性特征 细胞与细胞外基底膜相互作用(人 羊膜)，在没有或存在可能的抑制剂和增强剂的情况下。 这项为期三年的计划的具体目标是：(1)研究 侵袭前的细胞内和细胞表面的相互作用， 侵袭性和侵袭性后黑色素瘤细胞与基底的相互作用 (2)研究肿瘤细胞体外降解的机制。 确定特定类型(S)的纤溶酶原激活物(PA)和/或 激活剂和这些激活剂的生理抑制物产生 通过侵袭模型中的高转移和低转移变异；还可以测量 与细胞相关的PA活动量 膜；(3)研究抑制或刺激的大小 一种特定的生物反应调节剂--外源添加的影响 关于黑色素瘤的纤溶成分或这些成分的抗体 体外培养的肿瘤细胞(特别是它们的降解能力) 与细胞外屏障相互作用；以及(4)探索 参与肿瘤侵袭的某些细胞表面成分。这个 后者将包括使用单克隆抗体来高度转移 高转移性细胞表面抗原(细胞膜糖偶联物) 可能调节肿瘤细胞侵袭的细胞。

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.