Basic fibroblast growth factor released by single, isolated cells stimulates their migration in an autocrine manner.
Basic fibroblast growth factor (bFGF), a protein with angiogenic, mitogenic, and chemotactic properties, lacks a signal sequence and is not secreted via the classical secretory pathway. However, the growth factor is known to act extracellularly. Since no defined mechanism for bFGF release has been described, it has been suggested that this growth factor is released from dead or damaged cells. To test this hypothesis we characterized the effect of exogenously added bFGF and neutralizing antibody on the migration of single, isolated NIH 3T3 cells transfected with bFGF cDNA. Under these conditions the observed cell cannot be affected by bFGF derived from other cells. Cells were seeded onto colloidal gold-coated coverslips at a density of one cell per coverslip. A cell migrating on this substrate produces a track free of refringent gold particles that is measured by an image analyzer. The results showed that cell motility directly correlated with the amount of bFGF released from the migrating cells. Affinity-purified anti-bFGF antibody, but not irrelevant IgG, reduced the level of migration of the bFGF transfectants to that of the control cells transfected with the vector alone, showing that bFGF stimulates migration of the cell that releases it. Thus, bFGF is secreted by viable cells and mediates cell functions via a "true" autocrine mechanism.
Mignatti
P
P
Department of Cell Biology, New York University Medical Center, New York.
Morimoto
T
T
Rifkin
D B
DB
D016475:3T3 Cells; D000818:Animals; D000906:Antibodies; D002465:Cell Movement / Q000187:drug effects; D003001:Cloning, Molecular; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D014162:Transfection
D000906:Antibodies; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D013498:Suramin