CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.
The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway 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 percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression.
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Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
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D001483:Base Sequence; D001839:Bombesin / Q000032:analysis; D001980:Bronchi / Q000201:enzymology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000032:analysis*; D018004:Receptors, Bombesin / Q000032:analysis; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
D018004:Receptors, Bombesin; D014660:Vasoactive Intestinal Peptide; D015260:Neprilysin; D001839:Bombesin