Melanotransferrin

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Melanotransferrin (melanoma tumour antigen p97) is aniron-binding transferrin homologue expressed at highlevels on melanoma tumours and at lower levels on normaltissues. Unlike its relatives, transferrin and lactoferrin, melanotransferrin is membrane-bound. These properties suggest thatmelanotransferrin may assist melanoma and other tumour cell types withtheir increased requirement for iron. To address thishypothesis we utilised models including: (i) the melanotransferrinknockout mouse, and (ii) systematic down-regulation of melanotransferrin in melanoma cells using siRNA.Rigorous phenotypiccharacterisation of this knockout mouse demonstrated no differences in iron metabolism, behaviour or otherphysiological parameters compared to wild-typecontrols. In melanoma cells, melanotransferrin was found tofacilitate proliferation and migration, and also to enhance tumourigenesis in nudemice. Moreover, whole genome array analysis of these modelsin addition to cell models of melanotransferrin over-expressionindicated differences in genes associated with growth.

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