CD10/NEUTRAL ENDOPEPTIDASE-24.11 HYDROLYZES BOMBESIN-LIKE PEPTIDES AND REGULATES THE GROWTH OF SMALL-CELL CARCINOMAS OF THE LUNG

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD1O/neutral endopeptidase 24.11 (CD1O/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCCas is inhibited by CD1O/NEP and potentiated by CD1O/NEP inhibition. The results provide evidence that CD1O/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD1O/NEP, decreased cell surface CD1O/NEP enzymatic activity may be causally related to the development of SCCa of the lung.