Small cell lung cancer (SCLC) is a tumor enriched in its neuroendocrine properties. High levels of neurotransmitters, neural enzymes and polypeptide hormones are associated with SCLC. These polypeptide hormones include ACTH, calcitonin, vasopressin, physalaemin and bombesin-like peptides. Peptides may play an important regulatory role in SCLC and in particular, bombesin-like peptides function as autocrine growth factors in SCLC. Thus addition of an anti-bombesin monoclonal antibody inhibits the growth of SCLC in vitro and in vivo. Recently, neurotensin was found in high concentrations in SCLC cell lines and biopsy tissue.
The specific aims of this study are: 1) to determine factors which regulate the secretion of neurotensin from SCLC, 2) to characterize receptors for neurotensin on SCLC cells, 3) to investigate whether neurotensin induces second messenger production in SCLC cells and 4) to determine neurotensin levels in the blood of patients. The hypothesis of this study is that neurotensin functions as a regulatory peptide in SCLC. The long term objectives are to investigate the role of peptides in the development and regulation of SCLC. A variety of biochemical and pharmacological techniques will be employed. The levels of neurotensin will be determined by radioimmunoassay. Factors which stimulate and inhibit the secretion of neurotensin will be defined. Receptors for neurotensin will be characterized biochemically and the pharmacology of these receptors defined using synthetic neurotensin analogues. Biochemical techniques will be used to investigate if neurotensin induces second messenger production (cAMP, cGMP, Ca++ flux or phosphatidyl inositol turnover). Also, the role of neurotensin as a possible growth factor for SCLC will be investigated. Studies will indicate if neurotensin is elevated in the blood of patients with SCLC relative to control patients and if blood neurotensin levels may serve as useful biochemical markers in the diagnosis of SCLC. The results of these studies will provide a more comprehensive understanding of the properties of SCLC and the potential role of neurotensin as an important regulatory peptide in this disease.
