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 parathyroid-derived 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 FMEN1 plasmas [applied to heparin-Sepharose (HS) columns] in parathyroid-derived cloned endothelial cells. FMEN1 plasma HS-adsorbed activity exceeded normal plasma HS-adsorbed activity in 6 of 8 FMEN1 plasma samples. Peak (FMEN1 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 FMEN1 plasma prepared by gel filtration in 7 M urea displayed apparent mol wt of about 14-16 kD and showed increased apparent affinity for HS; recovered activity appeared principally in the 3.0-M NaCl eluate. Using a sensitive two-site immunoradiometric assay for bFGF we found 0.4 ng/mL bFGF-like immunoreactivity in the highly purified 3.0-M NaCl eluate from a HS column to which the active components from gel filtration of FMEN1 plasma in 7 M urea were applied. These results imply that bFGF or closely related factors circulate in FMEN1.
Zimering
M B
MB
Metabolic Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Brandi
M L
ML
deGrange
D A
DA
Marx
S J
SJ
Streeten
E
E
Katsumata
N
N
Murphy
P R
PR
Sato
Y
Y
Friesen
H G
HG
Aurbach
G D
GD
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D005260:Female; D005346:Fibroblast Growth Factors / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009377:Multiple Endocrine Neoplasia / Q000097:blood / Q000235:genetics* / Q000276:immunology; D009500:Neutralization Tests; D011863:Radioimmunoassay
D005346:Fibroblast Growth Factors