Production of gastrin-releasing peptide by a non-small 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 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.
Siegfried
J M
JM
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261.
Han
Y H
YH
DeMichele
M A
MA
Hunt
J D
JD
Gaither
A L
AL
Cuttitta
F
F
D001483:Base Sequence; D001839:Bombesin / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000648:ultrastructure; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D046508:Culture Techniques / Q000379:methods; D017931:DNA Primers; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000096:biosynthesis*; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000032:analysis; D010452:Peptide Biosynthesis; D010455:Peptides / Q000032:analysis; D011498:Protein Precursors / Q000096:biosynthesis; D011863:Radioimmunoassay; D018004:Receptors, Bombesin / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D005768:Gastrointestinal Hormones; D006133:Growth Substances; D009479:Neuropeptides; D010455:Peptides; D011498:Protein Precursors; D018004:Receptors, Bombesin; C047897:gastrin-releasing peptide precursor; D019886:Gastrin-Releasing Peptide; D001839:Bombesin