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All tumors contain a population of Cancer Stem Cells (CSCs) responsible for the initiation, growth and development of the tumor and a challenge in cancer research is their identification and eradication. In our laboratory, by chemical treatment of the human osteosarcoma MG63 cell line, we have isolated and characterized the human OS CSC line (3AB-OS). 3AB-OS CSCs have a significant chromosomal complexity and a large number of molecular abnormalities which appear to be strongly congruent with those described in a large number of pediatric and adult osteosarcomas. 3AB-OS cells transdifferentiated in vitro into cells of all three primary germ layers and, when xenografted in athymic mice they were highly tumorigenic and recapitulated in vivo crucial features of human osteosarcoma. They even expressed a reprogrammed energy metabolism, with a dependence on glycolytic metabolism more strong than parental MG63 cells. In comparison with parental MG63 cells (where TP53 gene is hypermethylated, rearranged and in single copy), 3AB-OS cells have TP53 gene unmethylated, rearranged and in multiple copies. Moreover, the mutp53 (p53-R248W/P72R) is post-translationally stabilized and with nuclear localization and has a gain of function. By a great number of results our findings suggested that p53 mutation could be the “driver mutation” at the root of the dedifferentiation of MG63 cells into 3AB-OS CSCs.

A short story of 3AB-OS Cancer Stem Cells, a possible model for studying cancer stemness