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Growth of Small Cell Lung Cancer Cells: Stimulation by Multiple Neuropeptides and Inhibition by Broad Spectrum Antagonists in Vitro and in Vivo¹

Imperial Cancer Research Fund, P. O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, England [T. S., E. R.], and ICRF Medical Oncology Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland [S. L., J. S.]

Neuropeptides are increasingly implicated in the control of cell proliferation and their mechanisms of action are attracting intense interest. The early complex cascade of events initiated by peptides of the bombesin family including gastrin-releasing peptide is increasingly understood. The cause-effect relationships and temporal organization of these early signals and molecular events provide a paradigm for the study of other growth factors and mitogenic neuropeptides and illustrate the activation and interaction of a variety of signaling pathways. These peptides may also act as autocrine growth factors for certain small cell lung cancer cells. The results discussed here strongly suggest that the autocrine growth loop of bombesin-like peptides may be only a part of an extensive network of autocrine and paracrine interactions involving a variety of Ca²⁺-mobilizing neuropeptides in small cell lung cancer including bradykinin, cholecystokinin, galanin, neurotensin, and vasopressin. In this context, broad spectrum antagonists that prevent the function of multiple Ca²⁺-mobilizing receptors are of special interest. These antagonists block neuropeptide mediated signals and inhibit small cell lung cancer growth in vitro and in vivo. Thus, broad spectrum neuropeptide antagonists constitute potential anticancer agents.