Siegfried J M, Han Y H, DeMichele M A, Hunt J D, Gaither A L, Cuttitta F
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261.
J Biol Chem. 1994 Mar 18;269(11):8596-603.
Gastrin-releasing peptide is an important growth-modulating factor in developing lung epithelium. It is known to be produced by small cell carcinomas of the lung, and an autocrine loop involving gastrin-releasing peptide and its receptor has been demonstrated in many small cell lung tumors. We investigated whether such an autocrine loop could also be demonstrated in non-small cell lung carcinoma, since gastrin-releasing peptide is known to stimulate human bronchial epithelial cells, from which non-small cell tumors should emerge. We report here that gastrin-releasing peptide is produced by a bronchiolo-alveolar carcinoma cell line (A549) adapted to serum-free and growth factor-free conditions. A549 cells adapted to these conditions, termed A549-R0 cells, display extensive membrane interdigitations, Golgi apparatus, and secretory-like granules, and grow as a mixture of attached colonies and floating cells. Gastrin-releasing peptide is present in the conditioned medium produced by A549-R0 cells. Colony formation of cells derived from a squamous cell carcinoma of the lung, 239T, was stimulated 9-fold by A549-R0 conditioned medium or by authentic gastrin-releasing peptide, measured in serum-free conditions. The growth stimulatory activity was inhibited by a monoclonal antibody to gastrin-releasing peptide. Transcripts for receptors for the bombesin family of peptides were also demonstrated in A549-R0 cells and 239T cells. These results demonstrate that non-small cell lung carcinomas can secrete gastrin-releasing peptide and can also respond to the peptide.
胃泌素释放肽是发育中的肺上皮细胞中一种重要的生长调节因子。已知它由肺小细胞癌产生，并且在许多小细胞肺癌中已证实存在涉及胃泌素释放肽及其受体的自分泌环。由于已知胃泌素释放肽可刺激人支气管上皮细胞，而非小细胞肿瘤应由此产生，因此我们研究了这种自分泌环是否也能在非小细胞肺癌中得到证实。我们在此报告，适应无血清和无生长因子条件的细支气管肺泡癌细胞系（A549）可产生胃泌素释放肽。适应这些条件的A549细胞，称为A549-R0细胞，表现出广泛的膜指状交错、高尔基体和分泌样颗粒，并以贴壁集落和悬浮细胞的混合物形式生长。胃泌素释放肽存在于A549-R0细胞产生的条件培养基中。在无血清条件下测定，来自肺鳞状细胞癌的239T细胞的集落形成受到A549-R0条件培养基或天然胃泌素释放肽的9倍刺激。生长刺激活性被抗胃泌素释放肽单克隆抗体抑制。在A549-R0细胞和239T细胞中也证实了蛙皮素家族肽受体的转录本。这些结果表明，非小细胞肺癌可以分泌胃泌素释放肽，并且也可以对该肽作出反应。
