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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2005-11-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558605800314 |
| _version_ | 1819036378672922624 |
|---|---|
| author | C. Parker Gibbs Valery G. Kukekov John D. Reith Olga Tchigrinova Oleg N. Suslov Edward W. Scott Steven C. Ghivizzani Tatyana N. Ignatova Dennis A. Steindler |
| author_facet | C. Parker Gibbs Valery G. Kukekov John D. Reith Olga Tchigrinova Oleg N. Suslov Edward W. Scott Steven C. Ghivizzani Tatyana N. Ignatova Dennis A. Steindler |
| author_sort | C. Parker Gibbs |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:04:34Z |
| format | Article |
| id | doaj.art-73f863f13f7b428799962048cdd246ef |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T08:04:34Z |
| publishDate | 2005-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-73f863f13f7b428799962048cdd246ef2022-12-21T19:10:50ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022005-11-0171196797610.1593/neo.05394Stem-Like Cells in Bone Sarcomas: Implications for TumorigenesisC. Parker Gibbs0Valery G. Kukekov1John D. Reith2Olga Tchigrinova3Oleg N. Suslov4Edward W. Scott5Steven C. Ghivizzani6Tatyana N. Ignatova7Dennis A. Steindler8Department of Orthopedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USADepartment of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USADepartment of Orthopedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USADepartment of Orthopedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USADepartment of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USADepartment of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USADepartment of Orthopedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USADepartment of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USAUF Shands Cancer Center, University of Florida, Gainesville, FL, USABone 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.http://www.sciencedirect.com/science/article/pii/S1476558605800314SarcomaStro-1self-renewalpluripotent Oct 3/4, Nanog |
| spellingShingle | C. Parker Gibbs Valery G. Kukekov John D. Reith Olga Tchigrinova Oleg N. Suslov Edward W. Scott Steven C. Ghivizzani Tatyana N. Ignatova Dennis A. Steindler Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis Neoplasia: An International Journal for Oncology Research Sarcoma Stro-1 self-renewal pluripotent Oct 3/4, Nanog |
| title | Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis |
| title_full | Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis |
| title_fullStr | Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis |
| title_full_unstemmed | Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis |
| title_short | Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis |
| title_sort | stem like cells in bone sarcomas implications for tumorigenesis |
| topic | Sarcoma Stro-1 self-renewal pluripotent Oct 3/4, Nanog |
| url | http://www.sciencedirect.com/science/article/pii/S1476558605800314 |
| work_keys_str_mv | AT cparkergibbs stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT valerygkukekov stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT johndreith stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT olgatchigrinova stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT olegnsuslov stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT edwardwscott stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT stevencghivizzani stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT tatyananignatova stemlikecellsinbonesarcomasimplicationsfortumorigenesis AT dennisasteindler stemlikecellsinbonesarcomasimplicationsfortumorigenesis |