The effect of novel iron chelators on iron-related Wnt signaling in animal cells

Iron is needed for the growth of all animal cells, being necessary for the proper function of several enzymesystems, the expression of certain important genes, and the production of oxygen radicals that help defendagainst microorganisms. Recent evidence suggests that iron also regulates Wnt signaling which is important fordiverse developmental processes. Given the key roles for iron in cell growth, cell migration, metabolism,respiration and host defense, a better understanding of iron uptake and its regulation by different animal celltypes could provide important new information as to the functioning of animal cells under normal and diseaseconditions. However, studies of iron requirements and the effects of iron withdrawal on animal cells have beenlimited by the lack of suitable model cell systems in which iron supply can be fully controlled and the lack ofiron-withdrawing agents that are more selective in their action. Chelation Partners Incorporated (CPI) hasdeveloped a new family of highly selective iron-withdrawing agents (iron chelators), and is interested todetermine whether these agents are able to affect Wnt signaling in animal cells. This collaborative researchproject will build on results obtained with the support of an earlier Engage grant. The Hoskin laboratory willuse novel iron-withdrawing agents from CPI to compare specific iron requirements for Wnt signaling in mouseversus human cell lines of differing cell types. Malignant counterparts of different healthy animal cells will beused to determine whether animal cells that have excessive Wnt signaling also have higher or more continuousiron requirements. A reporter cell system and western blotting will be used to determine the effect of irondeprivation on Wnt signaling. Quantitative real-time polymerase chain reaction will be used to determine effectof iron chelation on the expression of Wnt target genes This research will yield advance our understanding ofthe requirement for iron in Wnt signaling in animal cells and the effect of CPI iron-chelating compounds onthis essential signaling pathway. Being able to modulate Wnt signaling may have important biotechnology andbiomedical applications for Canada.