ABSTRACT
Small cell lung carcinoma (SCLC) is a neuroendocrine tumor that skills approximately 35,000 patients in the United States annually. The tumor is initially localized to the lung and then metastasizes to the bone, brain, liver, and lymph nodes. SCLC cells have dense-core neurosecretory granules reminiscent of neuronal synaptosomes. The peptides bind to G-protein-coupled receptors that contain approximately 400 amino acids and alter second-messenger production. Gastrin-releasing peptide (GRP), neuromedin B, pituitary adenylate cyclase activating peptide, Bradykinin, Vasopressin, neurotensin (NT), and cholecystokinin receptors stimulate phosphatidyl inositol turnover and elevate SCLC cytosolic Ca2+. High levels of bombesin/GRP were detected by radioimmunoassay. Because SCLC cells also contain immunoreactive NT, they can synthesize multiple neuropeptides. Opioid receptors and peptides are present in SCLC cell lines. SCLC cells have immunoreactive ß-endorphin and bind H-etorphin with high affinity to a single class of sites. It is generally accepted that agents that stimulate tyrosine kinase activity, such as insulin-like growth factor-I, regulate cancer proliferation.
