Shipp M A, Tarr G E, Chen C Y, Switzer S N, Hersh L B, Stein H, Sunday M E, Reinherz E L
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10662-6. doi: 10.1073/pnas.88.23.10662.
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 CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/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 CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.
蛙皮素样肽是许多肺小细胞癌（SCCas）重要的自分泌生长因子。在此，我们证明这些恶性肺神经内分泌细胞表达低水平的细胞表面金属内肽酶CD10/中性内肽酶24.11（CD10/NEP，常见急性淋巴细胞白血病抗原），且该酶可水解蛙皮素样肽。CD10/NEP可抑制依赖蛙皮素样肽的SCC生长，而抑制CD10/NEP则可增强其生长。这些结果提供了证据表明CD10/NEP参与肿瘤细胞增殖的调控。由于肺SCCa几乎仅发生于吸烟者，且香烟烟雾可使CD10/NEP失活，因此细胞表面CD10/NEP酶活性降低可能与肺SCCa的发生存在因果关系。
