PRODUCTION OF GASTRIN-RELEASING PEPTIDE BY A NONSMALL CELL LUNG-CARCINOMA CELL-LINE ADAPTED TO SERUM-FREE AND GROWTH FACTOR-FREE CONDITIONS

Gastrin-releasing peptide is an important growth-modulating factor in developing lung epithelium. It is known to be produced by small cell c arcinomas of the lung, and an autocrine loop involving gastrin-releasi ng peptide and its receptor has been demonstrated in many small cell l ung tumors. We investigated whether such an autocrine loop could also be demonstrated in non-small cell lung carcinoma, since gastrin-releas ing peptide is known to stimulate human bronchial epithelial cells, fr om which non-small cell tumors should emerge. We report here that gast rin-releasing peptide is produced by a bronchiolo-alveolar carcinoma c ell line (A549) adapted to serum-free and growth factor-free condition s. A549 cells adapted to these conditions, termed A549-R(0) cells, dis play extensive membrane interdigitations, Gels apparatus, and secretor y-like granules, and grow as a mixture of attached colonies and floati ng cells. Gastrin-releasing peptide is present in the conditioned medi um produced by A549-R(0) cells. Colony formation of cells derived from a squamous cell carcinoma of the lung, 239T, was stimulated 9-fold by A549-R(0) conditioned medium or by authentic gastrin-releasing peptid e, measured in serum-free conditions. The growth stimulatory activity was inhibited by a monoclonal antibody to gastrin-releasing peptide. T ranscripts for receptors for the bombesin family of peptides were also demonstrated in A549-R(0) cells and 239T cells. These results demonst rate that non-small cell lung carcinomas can secrete gastrin-releasing peptide and can also respond to the peptide.