title: Transferrin receptor-dependent and -independent iron transport in gallium-resistant human lymphoid leukemic cells.
abstract: Recent studies showed that gallium and iron uptake are decreased in gallium-resistant (R) CCRF-CEM cells; however, the mechanisms involved were not fully elucidated. In the present study, we compared the cellular uptake of 59Fe-transferrin (Tf) and 59Fe-pyridoxal isonicotinoyl hydrazone (PIH) to determine whether the decrease in iron uptake by R cells is caused by changes in Tf receptor (TfR)-dependent or TfR-independent iron uptake. We found that both 59Fe-Tf and 59Fe-PIH uptake were decreased in R cells. The uptake of 59Fe-Tf but not 59Fe-PIH could be blocked by an anti-TfR monoclonal antibody. After 59Fe-Tf uptake, R cells released greater amounts of 59Fe than gallium-sensitive (S) cells. However, after 59Fe-PIH uptake 59Fe release from S and R cells was similar. 125I-Tf exocytosis was greater in R cells. At confluency, S and R cells expressed equivalent amounts of TfR; however, at 24 and 48 hours in culture, TfR expression was lower in R cells. Our study suggests that the decrease in Tf-Fe uptake by R cells is caused by a combination of enhanced iron efflux from cells and decreased TfR-mediated iron transport into cells. Furthermore, because TfR-dependent and -independent iron uptake is decreased in R cells, both uptake systems may be controlled at some level by similar regulatory signal(s).
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Chitambar
authors.forename: J P
authors.initials: JP
authors.lastname: Wereley
mesh_terms: D001692:Biological Transport; D019008:Drug Resistance, Neoplasm; D005708:Gallium / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D011990:Receptors, Transferrin; D014168:Transferrin; D005708:Gallium