The goal of this research is to investigate the biological function of endogenous bombesin-like peptides in oat cell carcinoma. High levels of immunoreactive bombesin (BN) are present in 94% of the oat cell carcinoma cell lines examined. These BN-like peptides are secreted from oat cells in vitro by various stimuli such as K+ and agents such as theophylline or VIP which elevate the intracellular cAMP levels. In vivo BN-like peptides are elevated up to 40-fold in patients with extensive disease relative to control patients. Thus hypersecretion of BN-like peptides may account for some paraneoplastic syndromes associated with oat cell carcinoma such as anorexia. When released from oat cells these peptides may interact with receptors present on the cell surface. ?125?I-(Tyr?4?)BN was used as a receptor probe and it bound with high affinity (Kd = 0.5 nM) to a single class of sites (2,000/cell) using cell line NCI-H345 or NCI-H446. Binding was specific, saturable and reversible. Pharmacology studies indicated that the C-terminal octapeptide of BN or the structurally related gastrin releasing peptide was essential for binding. Biochemistry studies indicated that radio-labeled (Tyr?4?)BN may bind to a cell surface protein with a subunit molecular weight of 78,000 daltons. When activated by BN-like peptides these receptors induce growth of oat cells. Thus addition of exogenous BN (50 nM) in vitro stimulates growth of oat cells. In contrast, addition of an anti-BN monoclonal antibody inhibits growth of oat cell carcinoma in vivo and in vitro. Thus BN-like peptides may function as important autocrine growth factors in oat cell carcinoma. (2)
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