Missale C, Codignola A, Sigala S, Finardi A, Paez-Pereda M, Sher E, Spano P F
Department of Biomedical Sciences and Biotechnology, Division of Pharmacology, University of Brescia, Via Valsabbina 19, 25124, Brescia, Italy.
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5366-71. doi: 10.1073/pnas.95.9.5366.
Nerve growth factor (NGF) has antiproliferative and differentiating effects on adenomas of neuroendocrine origin. Cell lines derived from small-cell lung carcinoma (SCLC), a very aggressive neuroendocrine tumor, express NGF receptors. The role of NGF in the control of proliferation and progression of this carcinoma, however, has never been investigated. Chronic exposure of NCI-N-592 and GLC8 SCLC cell lines to NGF remarkably inhibited their proliferation rate both in vitro and in vivo, prevented their anchorage-independent clonal growth in soft agar, impaired their invasive capacity in vitro, and abolished their tumorigenic potential in nude mice. The proliferative response of SCLC cell lines to nicotine was also remarkably impaired by in vitro NGF treatment. Furthermore, NGF treatment activates in SCLC cell lines the expression and secretion of NGF. NGF thus reverts SCLC cell lines to a noninvasive, nontumorigenic phenotype that does not respond to nicotine and produces NGF.
神经生长因子（NGF）对神经内分泌起源的腺瘤具有抗增殖和分化作用。源自小细胞肺癌（SCLC）（一种极具侵袭性的神经内分泌肿瘤）的细胞系表达NGF受体。然而，NGF在这种癌症的增殖和进展控制中的作用从未被研究过。将NCI-N-592和GLC8 SCLC细胞系长期暴露于NGF，在体外和体内均显著抑制其增殖率，阻止其在软琼脂中不依赖贴壁的克隆生长，损害其体外侵袭能力，并消除其在裸鼠中的致瘤潜力。体外NGF处理也显著损害了SCLC细胞系对尼古丁的增殖反应。此外，NGF处理可激活SCLC细胞系中NGF的表达和分泌。因此，NGF使SCLC细胞系转变为一种对尼古丁无反应且产生NGF的非侵袭性、非致瘤性表型。
