BIOCHEMICAL-CHARACTERIZATION OF PEPTIDE ALPHA-AMIDATION ENZYME-ACTIVITIES OF HUMAN NEUROENDOCRINE LUNG-CANCER CELL-LINES

Peptide alpha-amidation is a posttranslational modification of approxi mately half of all endocrine and neuroendocrine peptide hormones, incl uding several hormones with mitogenic effects for tumor cells, and is typically essential for complete hormonal bioactivity. alpha-Amidated peptide hormones have been reported to be autocrine growth factors for small cell lung cancer cells. We report here that a variety of human lung tumor cell lines express both enzymes required for the two-step c onversion of inactive glycine-extended peptides into their active COOH -terminal alpha-amide analogues. Human tumor cell peptidylglycine alph a-amidation enzymes are present in multiple molecular forms. Both prot eins are metalloenzymes which are present af highest concentrations in secretory granules in neuroendocrine cell lines. The expression of th ese enzymes is positively correlated with expression of other markers of the neuroendocrine phenotype, such as DOPA decarboxylase. Peptidylg lycine alpha-amidating enzyme-specific activities are approximately 50 -fold higher in extracts of endocrine cell lines (lung small cell and carcinoid) than of nonendocrine lines. Biochemical characterization of the peptidylglycine alpha-amidating enzymes will enable development o f tools for detection of endocrine processes in the early stages of ne oplasia and for interruption of autocrine stimulation pathways in tumo r cells.