Circulating fibroblast growth factor-like autoantibodies in two patients with multiple endocrine neoplasia type 1 and prolactinoma.
Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. bFGF lacks a classical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bFGF-like mitogenic activity for parathyroid-derived endothelial cells and (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of subjects with multiple endocrine neoplasia type 1 (MEN-1). In the present study we examined the proliferative activity of MEN-1 and normal plasmas (applied to protein-A columns) in calf pulmonary artery endothelial 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 prolactinoma. 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 mol wt corresponding to those of the heavy and light chains of IgG. The IgG fraction of MEN-1 prolactinoma plasma had far more activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells. Endothelial cell bioactivity in protein-A-eluted fractions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit antibodies to intact bFGF. These results imply novel growth stimulatory bFGF-like autoantibodies in a subset of MEN-1 patients with prolactinoma.
Zimering
M B
MB
Veterans Affairs Medical Center, Lyons, New Jersey 07939.
Riley
D J
DJ
Thakker-Varia
S
S
Walker
A M
AM
Lakshminaryan
V
V
Shah
R
R
Brandi
M L
ML
Ezzat
S
S
Katsumata
N
N
Friesen
H G
HG
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002846:Chromatography, Affinity; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009377:Multiple Endocrine Neoplasia / Q000276:immunology*; D010911:Pituitary Neoplasms / Q000276:immunology*; D015175:Prolactinoma / Q000276:immunology*; D051381:Rats; D013205:Staphylococcal Protein A; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D016222:Fibroblast Growth Factor 2