Stro-1+ stromal cells have stem-like features in giant cell tumor of bone

Abstract

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. J. Surg. Oncol. 2012; 106:826-836. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.