MECHANISMS OF TUMOR CELL INVASION AND EXTRAVASATION

这项研究旨在提高我们对基本机制的理解， 肿瘤细胞外渗。 使用毛细血管内皮细胞单层和 在体外的原发性肿瘤细胞，我们将详细记录， 参与肿瘤的细胞表面成分：内皮附着。 与内皮细胞表面反应的单克隆抗体 成分，我们已经发现，以阻止肿瘤：内皮附着在 将研究体外阻断肺定殖的能力。 的 阻断效应的肿瘤特异性（或其缺乏）将是 确定以及所涉及的细胞表面组分的性质。 中性粒细胞或活化的巨噬细胞诱导 肿瘤增加：内皮附着，肿瘤在肺中的定位， 将研究肺定殖。 实际的生物化学性质 肿瘤细胞的基底膜基质降解将使用 分离的透镜囊用各种方法分析，包括电泳 和免疫印迹技术，以及基质降解与 使用相同的基质直接确定基底膜浸润 衬底 这些研究将包括使用选定的肿瘤变体 对于侵入穿过透镜囊基底膜的能力，宽 谱抗蛋白酶和互补蛋白酶抑制剂的混合物。 各种类型的白细胞对侵袭性 检查肿瘤细胞外渗的步骤。 除了这些研究的内在价值， 肿瘤发病机制，这些研究将提供相关的信息， 寻求阻断外渗的抗转移治疗的设计 迫使肿瘤栓子留在循环中。. . .天然 对他们不利的环境和一个非常适合治疗 操纵

This research seeks to improve our understanding of the basic mechanisms of tumor cell extravasation. Using capillary endothelial cell monolayers and primary tumor cells in vitro, we will document, in detail, the nature of the cell surface components involved in tumor:endothelial attachment. Those monoclonal antibodies reacting with endothelial cell surface components, which we have found to block tumor:endothelial attachment in vitro will be studied for the ability to block lung colonization. The tumor specificity (or lack thereof) of the blocking effect will be determined as well as the nature of the cell surface components involved. The mechanisms whereby neutrophils or activated macrophages can induce increased tumor:endothelial attachment, tumor localization in the lung and lung colonization will be investigated. The biochemical nature of actual basement membrane matrix degradation by tumor cells will be examined using isolated lens capsule analyzed in various ways including electrophoresis and immunoblot techniques, and the relationship of matrix degradation to basement membrane invasion directly determined using the same matrix substrate. These studies will include the use of tumor variants selected for the ability to invade across the lens capsule basement membrane, broad spectrum antiproteases and mixtures of complementary protease inhibitors. Possible contributions of various classes of leukocytes to the invasive steps of tumor cell extravasation will be examined. In addition to the intrinsic value of these studies to the understanding of tumor pathogenesis, these studies will provide information relevant to the design of antimetastatic therapies which seek to block extravasation forcing tumor emboli to remain in the circulation . . . . a naturally adverse environment for them and one which is very amenable to therapeutic manipulation.