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.
