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发现， 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， 在处理这种侵袭性疾病方面有希望的前景。 研究 旨在了解这种侵入性过程的生物学进展， 毫无疑问是有用的。 我们建议的总体目标 研究是进一步探索，在一个可靠的体外模型，我们有 开发，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;具体而言，异质性 高转移和低转移性黑色素瘤的侵袭特征 细胞，因为它们与细胞外基底膜（人 羊膜）在不存在和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 细胞内和细胞表面相关的相互作用， 侵袭性和侵袭后黑色素瘤肿瘤细胞与基底相互作用 膜的体外降解;（2）研究肿瘤细胞降解的机制， 鉴定纤溶酶原激活物（PA）的特定类型和/或 前活化剂和这些活化剂的生理抑制剂产生 通过侵袭模型中的高转移性和低转移性变体;此外， 与细胞相关的PA活性的量 （3）研究抑制性或刺激性的大小 特定生物反应调节剂的作用，外源性添加 纤维蛋白溶解成分或这些成分的抗体对黑色素瘤 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 某些参与肿瘤侵袭的细胞表面成分。 的 后者将包括使用单克隆抗体来高度转移 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。

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.