Transferrin Receptor-Dependent and -Independent Iron Transport in
Gallium-Resistant Human Lymphoid Leukemic Cells
Christopher R. Chitambar and
Janine P. Wereley
From the Division of Hematology/Oncology, Department of Medicine,
Medical College of Wisconsin, Milwaukee, WI.
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).
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4686-4693
© 1998 by The American Society of Hematology.
