Expression of transforming growth factors beta 1, beta 2, beta 3 in neuroendocrine tumors of the digestive system.

Neuroendocrine tumors of the digestive system are slowly growing neoplasms which often present pronounced fibrosis around tumor cells and in the peritoneal cavity. In this study, 23 midgut carcinoids and 7 endocrine pancreatic tumors were examined for the presence of TGF-beta with affinity-purified polyclonal antibodies raised against synthetic peptides coding for a specific region of latency-associated peptide sequences of TGF-beta 1, -beta 2, -beta 3, a rabbit anti serum against TGF-beta binding protein (LTBP) and a rabbit polyclonal antibody against TGF-beta type II-receptor (TGF-beta RII). Tumor cells from most tissues expressed all three isoforms of TGF-beta but LTBP was only weakly expressed. In stromal cells abundant expression of TGF-beta 2 and LTBP was found, whereas TGF-beta 1 and TGF-beta 3 were expressed only weakly. TGF beta RII immunoreactivity was observed mostly in the stromal cells. Tissue sections from 4 of these neuroendocrine tumors were also investigated by in situ hybridization. Strong signals on tumor cells were detected with TGF-beta 2 and TGF-beta 3 cRNA probes and also weakly with TGF-beta 1 and LTBP cRNA probe. Strong positive signals were observed on stromal cells with TGF-beta 2 and LTBP probe whereas only weak signals were observed on the stromal cells with TGF-beta 3 probe. Strong signals were detected on stromal cells with TGF-beta RII probe whereas no signals were observed on tumor cells. Our data suggest that TGF-beta might play an important role in the interaction of tumor and stromal cells. Thus TGF-beta might stimulate matrix production and angiogenesis of stromal cells, whereas tumor cells themselves are unaffected by the growth inhibitory activity of TGF-beta.