PROPERTIES OF EMERGING METASTATIC TUMOR CELL VARIANTS

转移，即恶性细胞从肿瘤组织中扩散和重建。 原发性肿瘤转移到远处器官，是目前最严重的问题。 癌症的临床管理。 未来的战略 转移的预防和控制必须面对现在， 确定的事实是肿瘤内的细胞不相同，或 静态，但能够持续变化，并且在以下方面差异很大 他们的转移潜能 肿瘤内的少数细胞 群体（转移性肿瘤细胞变体）具有极大的 夸大了转移扩散的可能性。 本提案中概述的研究的总体目标是 进一步描述了 发展中肿瘤内的转移性肿瘤细胞变体， 转移 这些研究现在可以通过开发 特异性单克隆抗体，可以区分转移性 非转移性肿瘤细胞的肿瘤细胞变体 同行 这种能力提供了一个独特的机会， 直接监测、分离和表征转移性变异体， 它们在原发肿瘤及其转移瘤内的自然环境。 这些研究的具体目标是：1）确定何时何地 转移性肿瘤细胞变异出现在原发性肿瘤中，为什么 转移性变体位于肿瘤脉管系统周围， 推进肿瘤前沿，2）检查免疫机制 以及肿瘤-宿主系统的后果， 和转移性肿瘤细胞变体的扩散，以及3）使用 重组DNA技术来推断 实验小鼠和人中的转移相关抗原 肿瘤，并检查其参与的调节机制， 表情 这些研究的其他长期目标是使用这些和其他 单克隆抗体快速筛选环境和 预防、引发或加速的治疗性病症 转移性变体形成。

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.