CIRCULATING FIBROBLAST GROWTH FACTOR-LIKE AUTOANTIBODIES IN 2 PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 AND PROLACTINOMA

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mit ogen found in a variety of normal and tumor tissues. bFGF lacks a clas sical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bF GF-like mitogenic activity for parathyroid-derived endothelial cells a nd (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of su bjects with multiple endocrine neoplasia type 1 (MEN-1). In the presen t study we examined the proliferative activity of MEN-1 and normal pla smas (applied to protein-A columns) in calf pulmonary artery endotheli al cells. Protein-A-eluted activity in plasma from MEN-1 prolactinoma plasma exceeded activity from normal and MEN-1 nonprolactinoma plasma in three of eight MEN-1 subjects with untreated or recurrent prolactin oma. Protein-A-eluted active fractions from MEN-1 prolactinoma plasma had several properties of an immunoglobulin G, including affinity for antihuman immunoglobulin G (IgG) agarose, sensitivity to thiols, and ( prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions) apparent mor wt corresponding to those of t he heavy and light chains of IgG. The IgG fraction of MEN-1 prolactino ma plasma had far mole activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prol actinoma cells. Endothelial cell bioactivity in protein-A-eluted fract ions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit anti bodies to intact bFGF. These results imply novel growth stimulatory bF GF-like autoantibodies in a subset of MEN-1 patients with prolactinoma .