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Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2009 May; Vol. 219 (2), pp. 301-13. - Publication Year :
- 2009
-
Abstract
- A novel cancer stem-like cell line (3AB-OS), expressing a number of pluripotent stem cell markers, was irreversibly selected from human osteosarcoma MG-63 cells by long-term treatment (100 days) with 3-aminobenzamide (3AB). 3AB-OS cells are a heterogeneous and stable cell population composed by three types of fibroblastoid cells, spindle-shaped, polygonal-shaped, and rounded-shaped. With respect to MG-63 cells, 3AB-OS cells are extremely smaller, possess a much greater capacity to form spheres, a stronger self-renewal ability and much higher levels of cell cycle markers which account for G1-S/G2-M phases progression. Differently from MG-63 cells, 3AB-OS cells can be reseeded unlimitedly without losing their proliferative potential. They show an ATP-binding cassette transporter ABCG2-dependent phenotype with high drug efflux capacity, and a strong positivity for CD133, marker for pluripotent stem cells, which are almost unmeasurable in MG-63 cells. 3AB-OS cells are much less committed to osteogenic and adipogenic differentiation than MG-63 cells and highly express genes required for maintaining stem cell state (Oct3/4, hTERT, nucleostemin, Nanog) and for inhibiting apoptosis (HIF-1alpha, FLIP-L, Bcl-2, XIAP, IAPs, and survivin). 3AB-OS may be a novel tumor cell line useful for investigating the mechanisms by which stem cells enrichment may be induced in a tumor cell line. The identification of a subpopulation of cancer stem cells that drives tumorigenesis and chemoresistance in osteosarcoma may lead to prognosis and optimal therapy determination. Expression patterns of stem cell markers, especially CD133 and ABCG2, may indicate the undifferentiated state of osteosarcoma tumors, and may correlate with unfavorable prognosis in the clinical setting.
- Subjects :
- ATP-Binding Cassette Transporters metabolism
Adolescent
Adult
Apoptosis physiology
Benzimidazoles metabolism
Biomarkers metabolism
Calcium Channel Blockers metabolism
Cell Differentiation physiology
Cell Line, Tumor physiology
Cell Shape
Child
Drug Resistance, Multiple physiology
Fluorescent Dyes metabolism
Gene Expression Regulation, Neoplastic
Humans
Neoplastic Stem Cells pathology
Osteosarcoma pathology
Rhodamine 123 metabolism
Verapamil metabolism
Young Adult
Benzamides pharmacology
Cell Line, Tumor drug effects
Enzyme Inhibitors pharmacology
Neoplastic Stem Cells drug effects
Neoplastic Stem Cells physiology
Osteosarcoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 219
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 19160414
- Full Text :
- https://doi.org/10.1002/jcp.21667