TY - JOUR
T1 - Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo
AU - Tirino, Virginia
AU - Desiderio, Vincenzo
AU - Paino, Francesca
AU - De Rosa, Alfredo
AU - Papaccio, Federica
AU - Fazioli, Flavio
AU - Pirozzi, Giuseppe
AU - Papaccio, Gianpaolo
PY - 2011/6
Y1 - 2011/6
N2 - This study aimed to identify, isolate, and characterize cancer stem cells from human primary sarcomas. We performed cytometric analyses for stemness and differentiation antigens, including CD29, CD34, CD44, CD90, CD117, and CD133, on 21 human primary sarcomas on the day of surgery. From sarcoma biopsies, we obtained 2 chondrosarcoma-stabilized cell lines and 2 osteosarcoma stabilized cell lines, on which sphere formation, side population profile, stemness gene expression, and in vivo and in vitro assays were performed. All samples expressed the CD133, CD44, and CD29 markers. Therefore, we selected a CD133 + subpopulation from stabilized cell lines that displayed the capacity to grow as sarcospheres able to initiate and sustain tumor growth in nonobese diabetic/severe combined (NOD/SCID) mice, to express stemness genes, including OCT3/4, Nanog, Sox2, and Nestin, and to differentiate into mesenchymal lineages, such as osteoblasts and adipocytes. Our findings show the existence of cancer stem cells in human primary bone sarcomas and highlight CD133 as a pivotal marker for identification of these cells. This may be of primary importance in the development of new therapeutic strategies and new prognostic procedures against these highly aggressive and metastatic tumors.
AB - This study aimed to identify, isolate, and characterize cancer stem cells from human primary sarcomas. We performed cytometric analyses for stemness and differentiation antigens, including CD29, CD34, CD44, CD90, CD117, and CD133, on 21 human primary sarcomas on the day of surgery. From sarcoma biopsies, we obtained 2 chondrosarcoma-stabilized cell lines and 2 osteosarcoma stabilized cell lines, on which sphere formation, side population profile, stemness gene expression, and in vivo and in vitro assays were performed. All samples expressed the CD133, CD44, and CD29 markers. Therefore, we selected a CD133 + subpopulation from stabilized cell lines that displayed the capacity to grow as sarcospheres able to initiate and sustain tumor growth in nonobese diabetic/severe combined (NOD/SCID) mice, to express stemness genes, including OCT3/4, Nanog, Sox2, and Nestin, and to differentiate into mesenchymal lineages, such as osteoblasts and adipocytes. Our findings show the existence of cancer stem cells in human primary bone sarcomas and highlight CD133 as a pivotal marker for identification of these cells. This may be of primary importance in the development of new therapeutic strategies and new prognostic procedures against these highly aggressive and metastatic tumors.
KW - Chondrosarcoma
KW - Osteosarcoma
KW - Sarcospheres
KW - Tumor-initiating cells
UR - http://www.scopus.com/inward/record.url?scp=79957883579&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957883579&partnerID=8YFLogxK
U2 - 10.1096/fj.10-179036
DO - 10.1096/fj.10-179036
M3 - Article
C2 - 21385990
AN - SCOPUS:79957883579
VL - 25
SP - 2022
EP - 2030
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 6
ER -