Stem-like cells in bone sarcomas: implications for tumorigenesis.
Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called "sarcospheres," in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES) cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44) as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.
Gibbs
C Parker
CP
Department of Orthopedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, 32611, USA. gibbscp@ortho.ufl.edu
Kukekov
Valery G
VG
Reith
John D
JD
Tchigrinova
Olga
O
Suslov
Oleg N
ON
Scott
Edward W
EW
Ghivizzani
Steven C
SC
Ignatova
Tatyana N
TN
Steindler
Dennis A
DA
D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D054278:Embryonal Carcinoma Stem Cells; D006801:Humans; D007150:Immunohistochemistry; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016895:Culture Media, Serum-Free; D017931:DNA Primers