CD1O NEP IN NONSMALL-CELL-LUNG CARCINOMAS - RELATIONSHIP TO CELLULAR PROLIFERATION/

The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (N EP) hydrolyzes a variety of peptide substrates and reduces cellular re sponses to specific peptide hormones. Because CD10/NEP modulates pepti de-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expre ssion in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and l arge cell carcinoma cell lines had low levels of CD10/NEP expression w hereas squamous, adenosquamous, and adenocarcinoma cell lines had high er and more variable levels of the cell surface enzyme. Regional varia tions in CD10/NEP immunostaining in primary NSCLC specimens prompted u s to correlate CD10/NEP expression with cell growth. In primary carcin omas of the lung, clonal NSCLC cell lines and SV40-transformed fetal a irway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest p ercentage of cells were actively dividing; in addition, these cells gr ew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell l ines had receptors for a variety of mitogenic peptides known to be CD1 0/NEP substrates, underscoring the functional significance of growth-r elated variability in CD10/NEP expression.