Hepcidin Expression in the Liver of Mice with Implanted Tumour Reacts to Iron Deficiency, Inflammation and Erythropoietin Administration

Cancer is known to be an important cause of anaemia due to several factors including iron deficiency and inflammation. Hepcidin, a key regulator of iron metabolism, is up-regulated by iron and inflammatory stimuli such as interleukin 6, and decreased by iron deficiency, enhanced erythropoiesis and hypoxia. It is supposed to play a crucial role in changes of iron metabolism in anaemia of chronic disease, which is characterized by sequestering iron in macrophages and decreasing its availability for red blood cell production. To study the effect of tumour growth on hepcidin expression, we implanted human melanoma cells into mice and studied the changes of the amount of liver hepcidin mRNA by real-time PCR. We observed development of anaemia, which correlated with the size of the tumour. Hepcidin expression significantly decreased with the anaemia development, but in late stages we observed an increase of its expression together with an increase of mRNA for interleukin 6. However, the increase of hepcidin expression could be inhibited by exogenous erythropoietin administration. In our model of tumour growth, hepcidin expression reflected anaemia development and iron deficiency, erythropoietin administration and inflammation, and we suppose that it could therefore serve as a useful marker of these clinical situations common in cancer patients and play a role in the pathogenesis of cancer-associated anaemia.