PROPERTIES OF EMERGING METASTATIC TUMOR CELL VARIANTS

恶性细胞的转移、扩散和重建 原发肿瘤转移到远处器官是最严重的问题 癌症的临床管理。中国的未来战略 预防和控制转移必须正视当下 确定的事实是肿瘤内的细胞不相同或 静态的，但能够持续变化，并且在 它们的转移潜能。肿瘤内的少数细胞 人群(转移性肿瘤细胞变种)拥有极大的 夸大了转移扩散的可能性。 这项建议中概述的研究的总体目标是 进一步描述了病毒的诱导、调节和传播 发展中肿瘤内的转移性肿瘤细胞变异 转移瘤。通过开发，这些研究现在是可能的 可以区分转移瘤的特异性单抗 来自非转移性肿瘤细胞的肿瘤细胞变体 对口单位。这一能力提供了一个独特的机会 直接监测、分离和鉴定转移变异体 它们在原发肿瘤及其转移瘤中的自然环境。 这些研究的具体目标是：1)确定时间和地点 原发肿瘤中出现转移性肿瘤细胞变异体及其原因 转移性变异体位于肿瘤血管周围， 肿瘤前沿进展，2)研究免疫机制 以及有利于肿瘤生长的肿瘤-宿主系统的后果 和转移性肿瘤细胞变种的扩散以及3)使用 利用重组DNA技术推断其一级结构 实验小鼠和人肿瘤转移相关抗原的研究 肿瘤，并研究它们的调控机制 表情。 这些研究的其他长期目标是使用这些和其他 用于快速筛查环境和环境的单抗 预防、启动或加速的治疗条件 转移性变异形成。

Metastasis, the spread and re-establish of malignant cells from the primary tumor to distant organs, is the most serious problem in the clinical management of cancer. Future strategies for the prevention and control of metastasis must confront the now established fact that cells within the tumor are not identical or static, but are capable of continual change and differ widely in their metastatic potential. A minority of cells within the tumor population (metastatic tumor cell variants) possess greatly exaggerated potential for metastatic spread. The overall goal of the studies outlined in this proposal is to further characterize the induction, regulation and spread of metastatic tumor cell variants within developing tumors and metastases. These studies are now possible through the development of specific monoclonal antibodies which can distinguish metastatic tumor cell variants from their non-metastasizing tumor cell counterparts. This capability presents a unique opportunity to directly monitor, isolate and characterize metastatic variants in their natural setting within the primary tumor and its metastases. Specific goals of these studies are 1) to determine when and where metastatic tumor cell variants arise in primary tumors, and why metastatic variants localize around the tumor vasculature and advancing tumor fronts, 2) to examine the immunological mechanisms and consequences of the tumor-host system which favor the outgrowth and spread of metastatic tumor cell variants and 3) to use recombinant DNA technology to deduce the primary structure of metastasis-associated antigens in experimental mice and human tumors, and examine the regulatory mechanisms involved in their expression. Other long term objects of these studies are to use these and other monoclonal antibodies to rapidly screen environmental and therapeutic conditions which prevent, initiate or accelerate metastatic variant formation.