Human osteosarcoma CD49f(-)CD133(+) cells: impaired in osteogenic fate while gain of tumorigenicity.

摘要: The biological relationships among self-renewal, tumorigenicity and lineage differentiation of human osteosarcoma-initiating cells (OSIC) remain elusive, making it difficult to identify distinguish OSIC from osteosarcoma-forming (OSFC) for developing OSIC-targeted therapies. Using a new inverse-lineage tracking strategy coupled with serial human-to-mouse xenotransplantation, we identified subpopulation osteosarcoma OSIC-like properties sought them their progeny, OSFC. We found that transplantation different cell lines primary tissues progressively increased the CD49f(+) composing bulk mass. These displayed characteristics OSFC: limited in vivo tumorigenicity, weak differentiation, more differentiated osteogenic feature greater chemo-sensitivity. By contrast, parental CD49f(-)CD133(+) had an inhibited fate, together strong progeny. Hence, phenotype appears possess correlated impaired fate ability initiate tumor growth through generation findings advance our understanding and, first time, provide much-needed distinction between OSFC this cancer.