The Role of Hepcidin in Anemia of Cancer

Anemia is a common occurrence in a wide variety of malignancies. When the anemia is not due to bleeding, bone marrow infiltration or chemotherapy, it is termed anemia of cancer (AC). AC is presumed to be a form of anemia of inflammation (AI, aka anemia of chronic disease). By limiting the availability of iron absorption from diet and release from stores, hepcidin causes AI. To test whether hepcidin contributes to AC, we created two syngeneic mouse models of lung cancer (TC-1 and LLC) and a syngeneic mouse model of melanoma (B16-F10). In all three models, significant anemia developed (Hgb 10.9±2.0, 9.1±2.0, 7.8±2.0 for TC-1, LLC, and B16-F10 vs. 13.7±1.2 for controls; p<0.001 for all compared to controls). There was no evidence of bleeding in the tumors or intraperitoneally. The anemia was microcytic in TC-1 mice but not LLC or B16-F10. Hepcidin mRNA (hepatic production measured by qRT-PCR) was increased in TC-1 mice but not LLC or B16-F10. To test whether hepcidin was necessary for the development of anemia in the TC-1 model, we generated tumors in hepcidin knockout mice. Hgb did not fall significantly in hepcidin knockout mice with TC-1 induced tumors (Hgb 14.5±2.4 vs. 15.5±2.2, p=0.3).

CONCLUSIONS: Hepcidin is necessary for the development of AC when hepcidin production is induced by the tumor and microcytosis is present. However, AC is likely a heterogenous disease; experiments are underway to determine whether hepcidin plays a role in cancers that do not upregulate hepcidin production or cause microcytosis.