A short story of 3AB-OS cancer stem cells, a possible modelfor studying cancer stemness

Cancer Stem Cells (CSCs) are thought to be the cause of cancer initiation, growth and development. Thus, achallenge in cancer research is their identification and eradication. In our laboratory, by chemical treatment of thehuman osteosarcoma (OS) MG63 cell line, we have isolated and characterized 3AB-OS cells, a human OS CSC line.3AB-OS cells transdifferentiate in vitro into cells of the three derivatives germ layers and, when xenografted in athymicmice they are highly tumorigenic and recapitulate in vivo crucial features of human OS. They even express areprogrammed energy metabolism, with a dependence on glycolytic metabolism more strong than parental MG63cells. 3AB-OS cells have chromosomes showing a great number of abnormalities which are very similar toabnormalities found in both pediatric and adult osteosarcomas. In comparison with parental MG63 cells (where TP53gene is hypermethylated, rearranged and in single copy), 3AB-OS cells have TP53 gene unmethylated, rearranged andin multiple copies. Moreover, the mutp53 (p53-R248W/P72R) is post-translationally stabilized, has nuclear localizationand a gain of function. A great number of results obtained in our laboratories suggested that p53 mutation could be the“driver mutation” at the origin of the transformation of MG63 cells into 3AB-OS CSCs.