Human carcinoid cell production of paracrine growth factors that can stimulate fibroblast and endothelial cell growth

A serotonin-secreting human pancreatic carcinoid cell line (BON) is demonstrated to express transcripts for all three mammalian types of transforming growth factor beta (TGF beta 1, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1991-10, Vol.51 (19), p.5253-5260
Main Authors: BEAUCHAMP, R. D, COFFEY, R. J, LYONS, R. M, PERKETT, E. A, TOWNSEND, C. M, MOSES, H. L
Format: Article
Language:English
Subjects:
Amino Acid Isomerases - biosynthesis
Biological and medical sciences
Blotting, Northern
Carcinoid Tumor - metabolism
carcinoma
Carrier Proteins - biosynthesis
Cell Division - physiology
cell growth
DNA - biosynthesis
Dose-Response Relationship, Drug
endothelium
Endothelium - parasitology
fibroblasts
Fibroblasts - pathology
Fibronectins - biosynthesis
Gastroenterology. Liver. Pancreas. Abdomen
growth factors
Growth Substances - biosynthesis
Humans
Insulin - pharmacology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
pancreas
Pancreatic Neoplasms - metabolism
paracrine
Peptidylprolyl Isomerase
Procollagen - biosynthesis
RNA, Messenger - biosynthesis
stimulation
Time Factors
Transcription, Genetic
Transforming Growth Factor alpha - biosynthesis
Transforming Growth Factor beta - biosynthesis
Tumors
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Summary:A serotonin-secreting human pancreatic carcinoid cell line (BON) is demonstrated to express transcripts for all three mammalian types of transforming growth factor beta (TGF beta 1, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three of the type-beta TGFs. Medium conditioned by BON cells had detectable TGF beta activity, although most of the activity was latent as determined by radioreceptor assay with and without prior acid treatment. However, nonactivated BON-conditioned medium stimulated DNA synthesis, soft agar growth, and an increase in TGF beta 1 and fibronectin mRNA expression in AKR-2B fibroblasts. In addition, BON-conditioned medium had a potent endothelial cell growth-stimulatory activity. Since the TGF beta s inhibit growth of endothelial cells, the presence of other growth factors was suspected. TGF alpha, c-sis, and basic fibroblast growth factor transcripts were also found to be expressed by the BON carcinoid cells. These data indicate that multiple peptide growth factors may have a paracrine role in the desmoplastic reaction accompanying carcinoid tumors.
ISSN:0008-5472
1538-7445