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Expression of Platelet-derived Growth Factor and Its Receptors in Neuroendocrine Tumors of the Digestive System¹

Department of Internal Medicine and Ludwig Institute for Cancer Research, University Hospital [A. C., V. P., K. Ö.], and Ludwig Institute for Cancer Research, Biomedical Center [C-H. H., K. F.], Uppsala, Sweden

Carcinoid tumors are slowly growing neuroendocrine neoplasms which often present pronounced fibrosis around the tumor cells. We have previously shown by immunohistochemistry that carcinoid tumors express platelet-derived growth factor (PDGF) ß-receptors on surrounding stromal cells. In this report, 22 midgut carcinoids and 5 endocrine pancreatic tumors were examined for the presence of PDGF with a monoclonal antibody raised against a peptide corresponding to a part of the B-chain of PDGF which reacts strongly with the B-chain and weakly with the A-chain. They were also examined for PDGF -receptors with an affinity-purified polyclonal peptide antibody and for PDGF ß-receptor with the monoclonal antibody PDGFR-B2. PDGF was expressed on tumor cells and on adjacent stroma. PDGF -receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas ß-receptors were seen only in the stroma. Tissue sections from some of these midgut carcinoids were also investigated by in situ hybridization for mRNA of PDGF A- and B-chains as well as - and ß-receptors. By in situ hybridization, abundant expression of mRNA for PDGF ß-receptor and PDGF A-chain was observed in stromal cells adjacent to carcinoid tumor cell clusters, but the mRNA expression in the tumor cells themselves was at a low level. A few clustered tumor cells and stromal cells expressed mRNA for the PDGF -receptor, thus consolidating the immunohistochemical findings. mRNA for the PDGF B-chain was detected in both tumor cells and stroma, but only at low levels. Our data suggest that PDGF is involved in the growth stimulation of the carcinoid tumor cells in an autocrine fashion and in the stimulation of stromal cell growth through paracrine and possibly autocrine mechanisms. Moreover, remarkably strong immunostaining of PDGF and the PDGF -receptor was seen on peripheral nerve fibers.

¹ This work was partly supported by the Swedish Medical Research Council and the Swedish Cancer Society.

² Present address: Transplantation Unit, Hippokratio, General Hospital, Alex, Papanastasiou 50, GR-546 39 Thessaloniki, Greece.

³ To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S-751 24 Uppsala, Sweden.

Received 7/17/91. Accepted 11/26/91.

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