Adaptive regulation of amino acid transport in nutrient-deprived human hepatomas

BACKGROUND: Malignant cells require increased amounts of amino acids, in particular glutamine and leucine, to support DNA and protein biosynthesis. Although plasma concentrations in the center of solid tumors can be much lower than normal circulating levels, it is still unknown how tumor cells can survive despite low amino acid levels. We examined the effects of glutamine or leucine deprivation on cell growth and amino acid transport activity in two human hepatoma cell lines, SK-Hep and HepG2. METHODS: We studied the transport of glutamine, leucine, alanine, and arginine. The carriermediated uptake of [sup.3]H-amino acids was determined in cells cultured in normal and amino acid-deprived media. RESULTS: The growth of both cell lines was dependent on the concentration of glutamine and leucine. In SK-Hep, there was a significant increase in initial rate glutamine transport activity in the glutamine-deprived group, attributable to an increase in transporter affinity (Km; 0.6 mmol/L [control], 385[+ or -]43 [mu]mol/L; 0.1 mmol/L, 221[+ or -]11[micro]mol/L; P