Circulating Fibroblast Growth Factor-Like Substance in Familial Multiple Endocrine Neoplasia Type 1*

Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. Basic FGF lacks a classical signal sequence, and it is not clear how it is released from cells. bFGF or bFGF-like activity has not been previously demonstrated in plasma. In an earlier study we showed increased mitogenic activity for parathyroidderived epithelial and mesenchymal cells in plasma of subjects with familial multiple endocrine neoplasia type 1 (FMEN1). In the present study we examined the growth-promoting activity of normal and FMENl plasmas [applied to heparin-Sepharose (HS) columns] in parathyroid-derived cloned endothelial cells. FMENl plasma HS-adsorbed activity exceeded normal plasma HS-adsorbed activity in 6 of 8 FMENl plasma samples. Peak (FMENl plasma) HS-adsorbed activity eluted with 0.1–0.3 m NaCl, was completely neutralized by specific antibodies against bFGF, and had an apparent mol wt of 110 kD. Active fractions from FMENl plasma prepared by gel filtration in ...