High and low affinity binding of heparin-binding growth factor to a 130-kDa receptor correlates with stimulation and inhibition of growth of a differentiated human hepatoma cell.
The differentiated human hepatoblastoma-derived cell line, HepG2, displayed two classes of specific membrane receptors for heparin-binding growth factor type 1 (HBGF-1). Specific membrane receptors were distinguished from nonreceptor heparin-like binding sites. Receptors with an apparent Kd of 9.2 +/- 0.9 pM and present at 15,000 +/- 900/cell correlated with HBGF-1 stimulation of HepG2 growth. Receptors with an apparent Kd of 2 +/- 0.4 nM and present at 180,000 +/- 18,000/cell correlated with inhibition of growth and changes in secretory products. Other hepatoma cell lines exhibited a simple positive mitogenic response to HBGF-1 and a single class of high affinity binding sites. HBGF-1 covalently cross-linked to hepatoma cell surface polypeptides of apparent mean molecular mass of 130 kilodaltons. At 37 degrees C, receptor-bound HBGF-1 was internalized (t 1/2 = 45 min) but not degraded for up to 6 h. The display of receptors decreased with increased cell density and expression of HBGF-1 mRNA and HBGF-1-like activity in the culture medium. Proliferating normal human hepatocytes also exhibited two classes of binding sites with affinities for HBGF-1 and apparent molecular weight similar to HepG2 cells. These results implicate HBGF-1 or homologues in human hepatoma cell growth and normal liver cell regeneration.
Kan
M
M
W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
DiSorbo
D
D
Hou
J Z
JZ
Hoshi
H
H
Mansson
P E
PE
McKeehan
W L
WL
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D013696:Temperature; D013997:Time Factors
D011975:Receptors, Mitogen; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D040262:Receptors, Vascular Endothelial Growth Factor