Stem-like cells in bone sarcomas: Implications for tumorigenesis

被引:393
作者
Gibbs, CP
Kukekov, VG
Reith, JD
Tchigrinova, O
Suslov, ON
Scott, EW
Ghivizzani, SC
Ignatova, TN
Steindler, DA
机构
[1] Univ Florida, Evelyn F & William L McKnight Brain Inst, Program Stem Cell Biol & Regenerat Med, Dept Neurosci, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Med, Dept Orthoped & Rehabil, Gainesville, FL 32610 USA
[3] Univ Florida, UF Shands Canc Ctr, Gainesville, FL 32610 USA
[4] Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA
[5] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
来源
NEOPLASIA | 2005年 / 7卷 / 11期
关键词
sarcoma; Stro-1; self-renewal; pluripotent Oct 314; Nanog;
D O I
10.1593/neo.05394
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 314 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.
引用
收藏
页码:967 / 976
页数:10
相关论文
共 32 条
  • [31] Identification of human brain tumour initiating cells
    Singh, SK
    Hawkins, C
    Clarke, ID
    Squire, JA
    Bayani, J
    Hide, T
    Henkelman, RM
    Cusimano, MD
    Dirks, PB
    [J]. NATURE, 2004, 432 (7015) : 396 - 401
  • [32] Further characterization of cells expressing STRO-1 in cultures of adult human bone, marrow stromal cells
    Stewart, K
    Walsh, S
    Screen, J
    Jefferiss, CM
    Chainey, J
    Jordan, GR
    Beresford, JN
    [J]. JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (08) : 1345 - 1356