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 /( (TGF01, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three of the type-0 TGFs. Medium conditioned by BON cells had detectable TGF0 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 TGF01 and fibronectin mRNA expression in AKR-2B fibroblasts. In addition, BONconditioned medium had a potent endothelial cell growth-stimulatory activity. Since the TGF/8s inhibit growth of endothelial cells, the presence of other growth factors was suspected. TGFa, c-.v/.v, 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.