Distinctive modulation of hepcidin in cancer and its therapeutic relevance

Abstract

Hepcidin, a short peptide synthesized primarily by hepatocytes in response to increased body iron and inflammation, is a crucial iron-regulating factor. Hepcidin regulates intestinal iron absorption and releases iron from macrophages into plasma through a negative iron feedback mechanism. The discovery of hepcidin inspired a torrent of research into iron metabolism and related problems, which have radically altered our understanding of human diseases caused by an excess of iron, an iron deficiency, or an iron disparity. It is critical to decipher how tumor cells manage hepcidin expression for their metabolic requirements because iron is necessary for cell survival, particularly for highly active cells like tumor cells. Studies show that tumor and non-tumor cells express and control hepcidin differently. These variations should be explored to produce potential novel cancer treatments. The ability to regulate hepcidin expression to deprive cancer cells of iron may be a new weapon against cancer cells.

Iron Metabolism in Cancer and Senescence: A Cellular Perspective

“…b. Hepcidin: a small peptide produced by the liver that is able to induce FPN1 degradation to block iron export from cells [8]. Hepcidin is overexpressed in several human tumors, such as breast, lung and prostate cancers, as well as multiple myeloma, for its property to promote neoplastic growth by increasing iron retention in malignant cells [147]. In a breast tumor microenvironment, cancer-associated fibroblasts stimulated hepcidin expression in breast cancer cells via the production of IL-6 [148], while it has been found that hepcidin expression is associated with immune tumor infiltrates in lung cancer, particularly those constituting B cells, CD4 + T cells, macrophages, neutrophils and dendritic cells [149].…”