physalaemin and Carcinoma--Small-Cell

Production and secretion of neuroendocrine peptides by small cell lung cancer (SCLC) has been detected in the past years. Most recently the role of bombesin as an autocrine/paracrine growth modifier has been demonstrated. We used the soft agarose clonogenic assay to evaluate the influence of other neuroendocrine peptides on the in vitro proliferation of SCLC cell lines. Neuroendocrine peptides tested were adrenocorticotropic hormone, arginine vasopressin, calcitonin, glucagon, kassinin, neurotensin, physalaemin, somatostatin, and substance P. Experiments were carried out in serum-free and serum-supplemented media with and without serum-free incubation periods. Our results indicated that the amphibian undecapeptide physalaemin inhibits the clonal and mass culture growth of SCLC cell lines at picomolar concentrations. All other neuroendocrine peptides failed to influence SCLC growth in the test systems used. These results suggest a growth regulating effect of physalaemin and a potential new form of neuroendocrine peptide therapy for SCLC.

Topics: Adrenocorticotropic Hormone; Arginine Vasopressin; Calcitonin; Carcinoma, Small Cell; Cell Division; Glucagon; Humans; Kassinin; Kinins; Neurotensin; Oligopeptides; Physalaemin; Somatostatin; Substance P

Topics: Animals; Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Humans; Hydrogen-Ion Concentration; Kinins; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Physalaemin; Radioimmunoassay; Transplantation, Heterologous

Immunoreactivity to the amphibian peptide physalaemin was characterized from extracts of a human lung small-cell carcinoma by immunological, chemical, and pharmacological means. Tumor-related peptide cross-reacted with three antiserums to physalaemin to yield 1.1 to 1.6 nanomoles per gram of tissue. Physalaemin and tumor peptide had similar retention times on high-performance liquid chromatography after chemical and enzymic modifications that included pH changes, oxone oxidation, use of a hydrophilic ion-pairing reagent, and digestion with trypsin and pyroglutamate aminopeptidase. Both physalaemin and the tumor peptide produced a contractile response of isolated guinea pig ileum at threshold concentrations of approximately 100 to 150 picograms per milliliter. These data suggest that small-cell carcinoma of the lung contains a physalaemin-like peptide that has structural and biological homology to its amphibian counterpart.

Topics: Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Cross Reactions; Humans; Immune Sera; Kinins; Lung Neoplasms; Oxidation-Reduction; Peptides; Physalaemin; Tachykinins