GLUTAMINE AS A REGULATOR OF DNA AND PROTEIN-BIOSYNTHESIS IN HUMAN SOLID TUMOR-CELL LINES

Objective The transport of glutamine by six different human solid tumo r-derived cell lines (e.g., breast, colon, liver) was characterized an d the impact of glutamine deprivation on rates of tumor cell prolifera tion and DNA and protein synthesis was assayed. Summary Background Dat a Glutamine is added routinely to cell culture media and its importanc e for cellular growth has been established. However, carrier-mediated glutamine transport by solid tumors has not been studied extensively, and the mechanisms by which glutamine contributes to cell growth regul ation require further investigation. Methods In a panel of different h uman solid tumor-derived cells, sodium-dependent glutamine transport w as characterized in vitro and rates of cell proliferation, protein and DNA synthesis, as well as thymidine transport, were correlated with g lutamine concentrations in the culture media. Results In all cells, re gardless of tissue origin, sodium-dependent glutamine transport was me diated almost exclusively by a single carrier. There was a range of Mi chaelis constants (Km) and maximal transport velocities (Vmax) for the glutamine transporter in each cell type, but the amino acid inhibitio n profiles were nearly identical, consistent with uptake by the System ASC family of transporters. Rates of cell growth, DNA and protein syn thesis, and thymidine transport correlated with the glutamine concentr ation in the culture media, indicating the central role of this amino acid in regulating cellular proliferation. Conclusions These data indi cate that glutamine transport by all solid tumors is mediated by the S ystem ASC family of transporters. The variation in Km values suggests that some cancers may be better suited to survive in a low glutamine e nvironment than others. The mechanism by which glutamine supports cell proliferation and regulates cell cycle kinetics involves its modulati on of DNA and protein biosynthetic rates.