Native and iron-saturated bovine lactoferrin differently hinder migration in a model of human glioblastoma by reverting epithelial-to-mesenchymal transition-like process and inhibiting interleukin-6/STAT3 axis

Glioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour spreading and dissemination. A number of actors, including cadherins, vimentin, transcriptional factors such as SNAIL, play critical roles in the EMT process. The interleukin (IL)-6/STAT3 axis has been related to enhanced glioblastoma's migration and invasion abilities as well. Here, we present data on the differential effects of native and iron-saturated bovine lactoferrin (bLf), an iron-chelating glycoprotein of the innate immune response, in inhibiting migration in a human glioblastoma cell line. Through a wound healing assay, we found that bLf was able to partially or completely hinder cell migration, depending on its iron saturation rate. At a molecular level, bLf down-regulated both SNAIL and vimentin expression, while inducing a notable increase in cadherins’ levels and inhibiting IL-6/STAT3 axis. Again, these effects positively correlated to bLf iron-saturation state, with the Holo-form resulting more efficient than the native one. Overall, our data suggest that bLf could represent a novel and efficient adjuvant treatment for glioblastoma's standard therapeutic approaches.