Ectopic Hepcidin Production in Anemia of Cancer

Abstract

Anemia is a frequent manifestation of almost all cancers. In some cases, the etiology of the anemia is clear (bleeding, bone marrow infiltration, or chemotherapy). When none of these factors are present, the anemia is referred to as anemia of cancer (AC). Hepcidin is a hormone synthesized in the liver that inhibits iron absorption from the diet and iron release from stores. In 2 patients with hepcidin secreting hepatic adenomas, AC resolved when the tumors were removed (Weinstein et al, Blood, 2002). However, it is unclear whether tumors not of hepatic origin can make hepcidin or whether this mechanism contributes to AC. We created two models of metastatic lung cancer by injecting two syngeneic lung cancer cell lines (TC‐1 and LCC) into the peritoneal cavities of C57Bl6 mice. Our data shows that hepcidin production is increased in both the liver and the tumor from TC‐1 injected mice. Inflammatory markers, SAA‐1 and FGN‐ã, are also elevated, indicating that the rise in hepatic hepcidin is likely due to inflammation. LLC‐injected mice developed less severe anemia and the increase in hepcidin mRNA was not significant. LLC tumors expressed measurable amounts of hepcidin but significantly less than TC‐1 tumors or control livers. Inflammatory induction of hepcidin likely plays an important role in AC. Some tumors express hepcidin, which could contributing to AC.