TUMOR DERIVED MEDIATORS IN BONE MARROW CELL GROWTH

研究建议的长期目标是增加我们的 了解细胞不同阶段的造血生理学知识 发展。在这项提案中，一种具有良好特征的小鼠模型 肿瘤诱导的粒细胞增多症将被用来理解 与某些肿瘤相关的粒细胞增多症。它的作用机制 粒细胞生成将在分子水平上进行研究，将 肿瘤的粒细胞生长因子对肿瘤来源的其他生长的影响 刺激间充质细胞增殖的因素。这个 多种类型的结缔组织细胞可能对 除了粒系祖细胞外，还将探索这种生长因子。 粒系造血因子的分离、鉴定及其活性 肿瘤衍生的其他生长因子将通过培养小鼠来实现 同时表现为粒系和粒系的乳腺癌细胞株 间充质细胞体外有丝分裂活性分析 通过体外生物测定释放到培养基中，并通过 生化分离活性蛋白质分子。物理和 这些生长因子的生化特性将被定义并 相互关联。该因素的生理相关性将通过以下方式进行调查 通过注入纯化因子进行体内实验，与纯化的 与荷瘤动物血清活性相关的因子及鉴定 利用放射性碘标记靶细胞和组织中的因子 蛋白。这些调查将提供重要的线索 了解肿瘤源性生长因子在宿主中的作用和 粒细胞的产生机制，进而提供了一种手段 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.