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.

细胞表面金属蛋白酶CD10/中性内肽酶24.11（NEP）水解多种肽底物，并降低细胞对特定肽类激素的反应。由于CD10/NEP调节肽介导的小细胞肺癌（SCLC）和正常胎儿支气管上皮的增殖，我们评估了该酶在非小细胞肺癌（NSCLC）中的表达。支气管肺泡癌和大细胞癌细胞系中CD10/NEP表达水平较低，而鳞状细胞癌、腺鳞癌和腺癌细胞系中这种细胞表面酶的水平较高且变化较大。原发性NSCLC标本中CD10/NEP免疫染色的区域差异促使我们将CD10/NEP表达与细胞生长相关联。在原发性肺癌、克隆性NSCLC细胞系和SV40转化的胎儿气道上皮中，部分细胞主要表达CD10/NEP或增殖细胞核抗原（PCNA）。当处于活跃分裂的细胞百分比最高时，培养的气道上皮细胞中CD10/NEP表达水平最低；此外，当细胞表面CD10/NEP被抑制时，这些细胞生长得更快。NSCLC细胞系具有多种已知为CD10/NEP底物的促有丝分裂肽的受体，这强调了CD10/NEP表达中与生长相关的变异性的功能重要性。