BACKGROUND: Giant cell tumor of bone (GCTB) is an aggressive benign bone tumor with poor prognosis whose neoplastic component is stromal cells (SCs). Tumor stem-like cells (TSCs) have been demonstrated as precursors for tumor genesis and growth. The aim of this study is to identify TSCs in GCTB. METHODS: Stro-1(+) and Stro-1(-) cells were isolated by fluorescence-activated cell sorting (FACS). Stem-like properties of both Stro-1(+) and Stro-1(-) subpopulations were assessed using MTT colorimetric assays, cell cycle analyses, sphere formation assays, and differentiation assays. Molecular profiles were analyzed by flow cytometry, immunofluorescence, and qRT-PCR. RESULTS: The existence of rare Stro-1(+) cells was confirmed in vitro using FACS and in vivo by immunohistochemistry. These Stro-1(+) cells exhibited higher proliferative and cisplatin-resistant potentials than Stro-1(-) cells. In serum-free suspension cultures, Stro-1(+) SCs could form cell spheres and maintain self-renewal. Furthermore, Stro-1(+) SCs could differentiate into two mesenchymal lineage cells: osteoblasts and adipocytes. Cell surface markers CD44, CD117, and CD133 and stem cell-associated genes OCT3/4, NANOG, and ABCG2 were significantly higher in the Stro-1(+) subpopulation. CONCLUSIONS: This study demonstrates that Stro-1(+) SCs in GCTB possess stem-like biological and molecular phenotypes, indicating that they are the TSCs of GCTB.
BACKGROUND:Giant cell tumor of bone (GCTB) is an aggressive benign bone tumor with poor prognosis whose neoplastic component is stromal cells (SCs). Tumor stem-like cells (TSCs) have been demonstrated as precursors for tumor genesis and growth. The aim of this study is to identify TSCs in GCTB. METHODS: Stro-1(+) and Stro-1(-) cells were isolated by fluorescence-activated cell sorting (FACS). Stem-like properties of both Stro-1(+) and Stro-1(-) subpopulations were assessed using MTT colorimetric assays, cell cycle analyses, sphere formation assays, and differentiation assays. Molecular profiles were analyzed by flow cytometry, immunofluorescence, and qRT-PCR. RESULTS: The existence of rare Stro-1(+) cells was confirmed in vitro using FACS and in vivo by immunohistochemistry. These Stro-1(+) cells exhibited higher proliferative and cisplatin-resistant potentials than Stro-1(-) cells. In serum-free suspension cultures, Stro-1(+) SCs could form cell spheres and maintain self-renewal. Furthermore, Stro-1(+) SCs could differentiate into two mesenchymal lineage cells: osteoblasts and adipocytes. Cell surface markers CD44, CD117, and CD133 and stem cell-associated genes OCT3/4, NANOG, and ABCG2 were significantly higher in the Stro-1(+) subpopulation. CONCLUSIONS: This study demonstrates that Stro-1(+) SCs in GCTB possess stem-like biological and molecular phenotypes, indicating that they are the TSCs of GCTB.
Authors: L Liu; E Aleksandrowicz; P Fan; F Schönsiegel; Y Zhang; H Sähr; J Gladkich; J Mattern; D Depeweg; B Lehner; J Fellenberg; I Herr Journal: Cell Death Dis Date: 2014-10-16 Impact factor: 8.469
Authors: Flavio Fazioli; Gianluca Colella; Roberta Miceli; Mariano Giuseppe Di Salvatore; Michele Gallo; Serena Boccella; Annarosaria De Chiara; Carlo Ruosi; Filomena de Nigris Journal: Oncotarget Date: 2017-06-28