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Human Carcinoid Cell Production of Paracrine Growth Factors That Can Stimulate Fibroblast and Endothelial Cell Growth¹

Department of Surgery [R. D. B., C. M. T.] and the Department of Human Biological Chemistry and Genetics [R. D. B.], The University of Texas Medical Branch, Galveston, Texas 77550; Departments of Medicine [E. A. P., R. J. C.], Pediatrics [E. A. P.], and Cell Biology [R. J. C., H. L. M.], Vanderbilt University, Nashville, Tennessee 37232; and Genetic Therapy, Inc., Gaithersburg, Maryland 20878 [R. M. L.]

A serotonin-secreting human pancreatic carcinoid cell line (BON) is demonstrated to express transcripts for all three mammalian types of transforming growth factor ß (TGFß1, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three of the type-ß TGFs. Medium conditioned by BON cells had detectable TGFß 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 TGFß1 and fibronectin mRNA expression in AKR-2B fibroblasts. In addition, BON-conditioned medium had a potent endothelial cell growth-stimulatory activity. Since the TGFßs inhibit growth of endothelial cells, the presence of other growth factors was suspected. TGF, 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.

¹ Supported by Public Health Service Grants CA01309 (R. D. B.), CA46413 (R. J. C.), CA48799 (H. L. M.), CA42572 (H. L. M.), and HL02776 (E. A. P.) and by a grant from the American Cancer Society, PDT-220 (C. M. T.).

² To whom requests for reprints should be addressed, at Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77550.

Received 3/29/91. Accepted 7/23/91.

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