Stimulation of HTC hepatoma cell growth in vitro by hepatic stimulator substance (HSS): Interactions with serum, insulin, glucagon, epidermal growth factor and platelet derived growth factor

Abstract

Hepatic stimulator substance (HSS), a partially purified extract of weanling or regenerating adult rat liver, is an organ-specific stimulator of liver growth in vivo and in vitro. The HTC hepatoma cell line is particularly responsive to HSS. The present experiments show that HSS will stimulate HTC cells in the complete absence of serum, although graded doses of fetal cal serum (FCS), from 0.1 to 5.0%, will increase the degree of stimulation in a dose-dependent manner. In contrast, when HSS is absent, increasing doses of FCS above 0.5% inhibit DNA synthesis. Much of this inhibition is removed by prior dialysis of the FCS and maximum enhancement of the HSS-induced stimulation occurs with only 0.1–0.5% of the dialysed FCS. Sera from older animals have less or even negative effect. Evidence is presented to show that the enhanced stimulation by HSS in the presence of serum is not due to insulin, glucagon, epidermal growth factor (EGF), or platelet derived growth factor (PDGF) and that HSS does not act via a shared receptor for one of these hormones. These experiments provide further evidence that HSS is a unique stimulator of liver growth and lend support to a model of organ-specific growth control.