The release of iron and transferrin from the human melanoma cell.
The role of the transferrin homologue, melanotransferrin (p97), in iron metabolism has been studied using the human melanoma cell line, SK-MEL-28, which expresses this antigen in high concentrations. The release of iron and transferrin were studied after prelabelling cells with human transferrin doubly labelled with iron-59 and iodine-125. Approx. 45% of internalised iron was in ferritin with little redistribution during reincubation. Iron release was linear with time, while transferrin release was biphasic, suggesting that iron was leaving the cell independently of transferrin. Unlabelled diferric transferrin increased transferrin release, implying a degree of coupling between cell surface binding, internalisation and release of transferrin. Increasing the preincubation time increased the amount of transferrin which remained internalised within the cell. A membrane-bound, iron-binding component with properties consistent with melanotransferrin was observed. Desferrioxamine or pyridoxal isonicotinoyl hydrazone could not remove iron from this compartment, suggesting a high affinity for iron. The number of membrane iron-binding molecules per cell was estimated to be 387,000 +/- 7000 . The non-transferrin-bound membrane Fe did not decrease during reincubation periods up to 5 h, suggesting that the cell was not utilising it. Hence, melanotransferrin may not have a role in internalising iron in melanoma cells.
Richardson
D R
DR
Department of Physiology, University of Western Australia, Nedlands.
Baker
E
E
D000951:Antigens, Neoplasm; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008545:Melanoma; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000378:metabolism*; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*
D000951:Antigens, Neoplasm; D007502:Iron Chelating Agents; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014168:Transferrin; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D007501:Iron; D003676:Deferoxamine; D007538:Isoniazid