TUMOR DERIVED MEDIATORS IN BONE MARROW CELL GROWTH

这项研究计划的长远目标是增加我们的 造血细胞各阶段生理学知识 发展 在这个提议中，一个良好表征的小鼠模型， 肿瘤诱导的粒细胞增多症将被用来了解的机制， 与某些肿瘤有关的粒细胞增多症。 的机理 将在分子水平上研究粒细胞生成， 肿瘤的粒细胞生成生长因子对肿瘤衍生的其他生长 刺激间充质细胞增殖的因子。 的 多种类型的结缔组织细胞可能会对 将探索除粒细胞祖细胞之外的该生长因子。 粒细胞生成因子的分离和表征以及 肿瘤衍生的其它生长因子将通过培养鼠 一种乳腺癌细胞系，其显示出粒细胞生成和 体外间充质细胞促有丝分裂活性，分析活性 通过体外生物测定释放到培养基中， 生物化学分离活性蛋白质分子。 物理和 这些生长因子的生物化学性质将被定义， 相关的 将通过以下方法研究该因素的生理相关性： 通过输注纯化的因子进行的体内实验， 因子与荷瘤动物血清活性的关系， 靶细胞和组织的因子通过使用放射性碘标记 蛋白 这些调查将提供一个重要的线索， 了解肿瘤源性生长因子在宿主中的作用， 粒细胞产生的机制，并反过来将提供一种手段， 进一步剖析某些肿瘤产生生长因子的机制。

The long term objectives of the research proposal is to increase our knowledge in physiology of hemopoiesis at various stages of cell development. In this proposal, a well characterized murine model of tumor-induced granulocytosis will be used to understand the mechanism of granulocytosis associated with certain tumors. The mechanism of granulopoiesis will be investigated at the molecular level by relating the tumor's granulopoietic growth factor to the tumor-derived other growth factors which stimulate proliferation of mesenchymal cells. The possibilities that multiple types of connective tissue cells may respond to this growth factor in addition to granulocyte progenitors will be explored. Isolation and characterization of the granulopoietic factor as well as tumor-derived other growth factors will be achieved by culturing a murine mammary carcinoma cell line which demonstrates both granulopoietic and mesenchymal cell mitogenic activities in vitro, analyzing the activities released into the culture medium by in vitro bioassays, and by biochemically separating the active protein molecules. Physical and biochemical properties of these growth factors will be defined and correlated. Physiological relevance of the factor will be investigated by in vivo experiments by infusions of purified factor, relating the purified factor with serum activities of tumor bearing animals and by identifying the target cells and tissue of the factor by the use of radio iodinated protein. These investigations would provide an essential clue in understanding the role of tumor derived growth factors in hosts and the mechanism of granulocyte production, and, in turn would provide a means to further dissect the mechanism of growth factor production by certain tumors.