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Production of gastrin-releasing peptide by a non-small cell lung carcinoma cell line adapted to serum-free and growth factor-free conditions
Ist Teil von
The Journal of biological chemistry, 1994-03, Vol.269 (11), p.8596-8603
Ort / Verlag
Bethesda, MD: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1994
Quelle
MEDLINE
Beschreibungen/Notizen
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.