The development and progression of a malignant tumor is a process which involves several essential interactions with the vasculature. Cells in the primary tumor must attract new blood vessels in order to grow beyond a small spheroid and these vessels then provide a conduit for the exit of cells that may progress to become secondary colonies in nearby or distant organs. Tumor cell that travel via the blood stream to distant organs must again interact with the vasculature in order to escape from the blood stream and invade the tissue at the secondary site. In many cases there is a selectivity between certain types of metastatic tumors and the organs that they preferentially colonize. The goal of this proposal is to examine the interactions between tumor cells and blood vessels that may lead to the colonization of specific organ sites. These interactions include the adhesion of tumor cells to specific adhesive determinants, the migration of tumor cells to specific chemotactic determinants and the modulation of tumor cell growth by organ-specific mitogens or growth inhibitors. The goal of this proposal is to isolate and identify cell adhesion and migration- stimulating molecules that may influence the colonization of lung and liver tissue by metastatic tumor cells. Tumor cell receptors to these adhesion and chemotactic molecules will also be characterized. These adhesive and chemotactic molecules will be isolated from whole tissue and from isolated microvessels using a variety of chromatographic techniques. Antibodies raised against the purified molecules will be used to determine the distribution of these factors within the tissues of interest and to determine their localization relative to the organ vasculature. The isolated factors and the antibodies raised against them will then be used in experiments conducted in vivo to attempt to modulate pre- existing patterns of organ-specific tumor colonization.
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