Oat cell carcinoma, or small cell lung cancer (SCLC), is a tumor enriched in its neuroendocrine properties. High levels of enzymes, such as neuron specific enolase and dopamine decarboxylase, and polypeptide hormones are associated with SCLC. In particular, high levels of bombesin(BN)-like peptides are found in SCLC cells, tumors and xenographs in nude mice. BN-like peptides are secreted from SCLC cells when the cells are depolarized and SCLC cells have receptors for BN-like peptides. BN stimulates the growth of SCLC cells. Thus BN-like peptides may function as important growth factors in oat cell carcinoma. The underlying hypothesis of this study is the BN-like peptides function as autocrine growth factors in SCLS. The long term objective is to define the role of BN-like peptides in oat cell carcinoma.
The specific aims are: 1) To determine what factors regulate the secretion of BN-like peptides. 2) To isolate and characterize the cellular receptors for BN-like peptides. 3) To determine the mechanism of action of BN-like peptides in SCLC cells. 4) To determine if antibodies, other factors or BN receptor antagonists can act as inhibitors of the growth of oat cells. A variety of biochemical, pharmacological and immunological techniques will be employed. The levels of BN-like peptides will be determined by radioimmunoassay. Specifically, factors which inhibit the secretion of BN-like peptides will be defined. Receptors for BN-like peptides will be solubilized and purified. Anti-receptor antibodies will be generated and tested for their ability to inhibit SCLC growth. Biochemical techniques will be used to investigate the ability of BN-like peptides to alter Ca++-flux, cGMP production and phosphatidyl inositol turnover with the goal of defining BN-receptor antagonists. The results of these studies will provide a more comprehensive understanding of the properties of SCLC cells and may yield new therapeutic approaches in the form of agents which inhibit the growth of oat cell carcinoma.
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