Transferrin reverses the anti-invasive activity of human prostate cancer cells that overexpress sema3E.

In vitro invasion and adhesion of stably semaphorin (sema) 3E-transfected PC-3 prostate cancer cells were determined in the presence and absence of transferrin. Invasion and adhesion decreased compared to untransfected cells; however, transferrin reversed the effects. Transferrin differentially regulated E-cadherin and beta-catenin in these cells. Insulin growth factor 3 (IGFBP3) negated the invasive and adhesive effects of transferrin. Transferrin increased binding of insulin growth factor (IGF)-1 to the activated IGF-1 receptor, and IGF-1 mimicked the invasive and adhesive effects of transferrin. These data suggest that transferrin modulates sema3E-transfected cells through an IGFBP3/IGF-1-dependent pathway, in part, by regulation of adhesion proteins.