FGF-1 is a heparin-independent mitogen for rat hepatocytes

We have found that in the primary culture of rat hepatocytes, the potent mitogenic activity of native FGF-1 is independent of heparin. The well-established characteristic of FGF-1 as a heparin-dependent mitogen is confirmed by human umbilical vein endothelial cells using the same preparation of FGF-1. Cross-linking experiments reveal that binding of FGF-1 to the hepatocyte cell surface receptors can be accomplished in the absence of exogenous heparin, in contrast to human endothelial cells for which it remains as a limiting factor. For both cell types, however, it is demonstrated that either endogenous or exogenous heparan sulfate/heparin moieties are essential for FGF-1 to establish receptor binding and mitogen action. Thus, the results suggest that hepatocytes harbor cell surface heparan sulfate moieties that are fully capable of utilizing FGF-1 in the environment. These results raise the possibility that FGF-1 is of differential potency for different cell types according to the nature and/or quantity of cell surface heparan sulfate moieties in vivo.