Research ArticleBreast Cancer

Ferroportin and Iron Regulation in Breast Cancer Progression and Prognosis

Science Translational Medicine  04 Aug 2010:
Vol. 2, Issue 43, pp. 43ra56
DOI: 10.1126/scitranslmed.3001127

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Iron: Out of Control in Cancer

Toddlers cause an awful lot of damage if let loose without an adult to control their behavior. The same is true for the body’s iron, which when released from its usual protein-binding partners can wreak toxic havoc. Thus, cells usually have an elaborate regulatory system to keep this essential but dangerous metal under control—except for some cancer cells, which have too little of an iron export protein called ferroportin. Pinnix et al. now show that breast cancers with low concentrations of ferroportin tend to contain extra intracellular free iron and to show signs of being more aggressive, suggesting that abnormal iron regulation in cancers may contribute to malignancy.

In an array of normal and cancerous breast epithelial cells, the authors showed that cells with less ferroportin and more of a ferroportin regulator called hepcidin tended to be aggressive. To confirm that the lower ferroportin and higher intracellular free iron actually affected tumor growth, they implanted mice with cancer cells identical except for the addition of extra ferroportin to bring the level of ferroportin in cancer cells to a level near that of normal breast cells. The additional ferroportin in this set of tumors inhibited their growth. In patients, too, the ferroportin status of breast cancer cells proved informative. Women who had breast cancers with lower ferroportin survived for shorter times, and the ferroportin concentrations of a particular tumor could be used to predict survival, providing information beyond the existing markers used clinically such as the estrogen receptor. The authors also came to a more positive conclusion: Having breast cancer with high ferroportin concentrations is a promising sign for a patient and predicts a 90% 10-year survival rate.

Ferroportin, as a marker for iron regulation, may be useful prognostically and in treatment planning. Although it is not yet apparent exactly how higher concentrations of free iron may cause cancer cells to be more aggressive, the cellular iron-regulatory system is clearly a key to understanding breast, and possibly other, cancers. When iron gets out of control, it seems to cause quite a bit of trouble.


  • Citation: Z. K. Pinnix, L. D. Miller, W. Wang, R. D’Agostino Jr., T. Kute, M. C. Willingham, H. Hatcher, L. Tesfay, G. Sui, X. Di, S. V. Torti, F. M. Torti, Ferroportin and iron regulation in breast cancer progression and prognosis. Sci. Transl. Med. 2, 43ra56 (2010).