Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

Abstract Background : Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies has increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer initiating cells and slow cellular cycle cells, identified by their capacity to retain long labelling (LT+). Methods : In this study, we perform tumour cell culture dose-response assays in adherent and mamospheres cultures. We also probe our conclusion in Xenograft models. Cell culture and in vivo tumours were analysed by immunofluorescence, qPCR and flow cytometry assays showing how stem cell self-renewal modulating proteins, such as PEDF, can statistically significant modify the properties, cell-percentage expressing biomarkers, and carcinogenicity of cancer stem cells (by student t-test). Results : The PEDF signaling pathway could be a useful tool for controlling cancer stem cells’ self-renewal, and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells in vitro culture. We have designed a peptide consisting in the C-terminal part of this protein, which acts by blocking endogenous PEDF in culture cell assays. Conclusion : We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against Docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this PEDF-modified protein produces a significant decrease in the percentage of cancer stem cell expressing markers.