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Research Article Free access | 10.1172/JCI117526

CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

R K Ganju, M Sunday, D G Tsarwhas, A Card, and M A Shipp

Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

Find articles by Ganju, R. in: JCI | PubMed | Google Scholar

Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

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Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

Find articles by Tsarwhas, D. in: JCI | PubMed | Google Scholar

Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

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Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

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Published November 1, 1994 - More info

Published in Volume 94, Issue 5 on November 1, 1994
J Clin Invest. 1994;94(5):1784–1791. https://doi.org/10.1172/JCI117526.
© 1994 The American Society for Clinical Investigation
Published November 1, 1994 - Version history
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Abstract

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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Referenced in 2 patents
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