Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia.
The iron-regulatory hormone hepcidin has been proposed as the mediator of anemia of inflammation (AI). We examined the acute and chronic effects of hepcidin in the mouse. Injections of human hepcidin (50 microg/mouse), but not of its diluent, induced hypoferremia within 4 hours. To examine the chronic effects of hepcidin, we implanted either tumor xenografts engineered to overexpress human hepcidin or control tumor xenografts into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Despite abundant dietary iron, mice with hepcidin-producing tumors developed more severe anemia, lower serum iron, and increased hepatic iron compared with mice with control tumors. Hepcidin contributes to AI by shunting iron away from erythropoiesis and sequestering it in the liver, predominantly in hepatocytes.
Rivera
Seth
S
Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA. sethrivera@mednet.ucla.edu
Liu
Lide
L
Nemeth
Elizabeta
E
Gabayan
Victoria
V
Sorensen
Ole E
OE
Ganz
Tomas
T
D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000209:etiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D004334:Drug Administration Schedule; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000037:antagonists & inhibitors / Q000097:blood*; D019266:Iron, Dietary / Q000008:administration & dosage / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000150:complications* / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000150:complications* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods / Q000473:pathology; D014183:Transplantation, Heterologous / Q000473:pathology; D014412:Tumor Virus Infections / Q000097:blood / Q000150:complications / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D019266:Iron, Dietary; D007501:Iron