Iron is ubiquitous in the human body, fulfilling many crucial roles. However, accumulating evidence implicates excess iron as a carcinogen. This study aimed to further investigate the role of iron and haem in breast carcinogenesis and the potential utility of chelators in therapy. We demonstrate that the transport machinery for iron and haem is dysregulated in breast cancer, with import being promoted and export down-regulated to allow the accumulation of intra-cellular iron. In vitro studies demonstrate that, in contrast to benign cells, malignant cells are capable of importing haem as well as ionic iron. Both iron and haem stimulate aggressive behaviour in malignant cells, up-regulating viability, proliferation, adhesion, migration and invasion. These changes are abrogated by iron chelation. In addition, the expression profile of iron and haem transporters is shown to favour intra-cellular accumulation even when iron is plentiful and import would be expected to be down-graded. Overall this study suggests that breast cancer may be due to an inappropriate expression profile of iron and haem transporters, leading to excess intra-cellular iron which drives a malignant cell phenotype. In addition the action of chelators to downgrade malignant behaviour implies a potential therapeutic role.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:667813 |
| Date | January 2015 |
| Creators | Roe, Thomas |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/6233/ |
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