Mechanism Study On The Role Of Trace Element Iron In Migration Of Human Breast Cancer Cells

Trace metal element iron is involved in many vital events. However, if iron isoverloaded in organism, the risk of cancer will be increased. Tumor metastasis is thecause for the death of breast cancer patients. The mechanism of the role of iron intumor metastasis is not clear, especially in breast cancer metastasis.In this investigation, we studied the relationship between iron and migration inhuman breast cancer cells and explored the possible mechanism involved.MDA-MB-231cells which are more aggressive with a mesenchymal phenotype, andMCF-7cells which are relatively benign with an epithelial phenotype were used asthe experimental objects. Iron chelator deferoxamine (DFO) was used to disturb ironhomeostasis. To directly study intracellular iron concentration and distribution in thesingle cell, synchrotron radiation X-ray fluorescence elemental mapping was used.Correspondingly, the expression of certain related proteins was analyzed usingwestern blot and immunofluorescence staining. Our results showed that after DFOtreatment, iron concentration was increased in MDA-MB-231cells, while decreased inMCF-7cells, and many particles which were rich of iron were found both inside andoutside of MDA-MB-231cells. With the change of intracellular iron concentrationafter DFO treatment, the migration capacity of MDA-MB-231cells was enhanced,while no significant difference was found in MCF-7cells. The mechanism researchshowed activating NF-κB and TGF-β/Smad signaling pathways promotedMDA-MB-231cells migration through regulating the expression of vimentin.Our study suggested that iron took part in breast cancer cell migration and ironchelator DFO had distinct functions based on different types of human breast cancercells. Highly aggressive breast cancer cells had a stronger capacity for capturing ironthan benign ones to increase iron transport in cells through various ways in ironstarvation state, and the increased total intracellular iron promoted cancer cellsmigration capacity by activating some related signaling pathways.