Reduced expression of INK4a/ARF genes in stem-like sphere cells from rat sarcomas

The presence of cancer stem cells, in both hematopoietic and solid malignancies, has been recently linked to their pathogenesis. We aimed to identify the characteristics and stem-like properties of sphere-colony forming cells in rat osteosarcoma and malignant fibrous histiocytoma cell lines. The res...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-10, Vol.362 (3), p.773-778
Main Authors: Fujii, Hiromasa, Honoki, Kanya, Tsujiuchi, Toshifumi, Kido, Akira, Yoshitani, Kazuhiro, Mori, Toshio, Takakura, Yoshinori
Format: Article
Language:English
Subjects:
Animals
Bmi1
Cancer stem cell
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p16 - chemistry
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
DNA Primers - chemistry
Gene Expression Regulation, Neoplastic
Histiocytoma, Malignant Fibrous - metabolism
Malignant fibrous histiocytoma
Microscopy, Phase-Contrast
Neoplasm Metastasis
Osteosarcoma
Osteosarcoma - metabolism
Osteosarcoma - pathology
p16 INK4a
p19 ARF
Phenotype
Rat
Rats
Sarcoma - metabolism
Stat3
STAT3 Transcription Factor - metabolism
Stem Cells - cytology
Stem Cells - metabolism
Tumor Suppressor Protein p14ARF - metabolism
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Summary:The presence of cancer stem cells, in both hematopoietic and solid malignancies, has been recently linked to their pathogenesis. We aimed to identify the characteristics and stem-like properties of sphere-colony forming cells in rat osteosarcoma and malignant fibrous histiocytoma cell lines. The results showed that both cell lines possessed an ability to form spherical, clonally expanding colonies in anchorage-independent, serum-starved conditions in N2/1% methylcellulose medium. The sphere cells showed stem-like properties with the ability to self-renew, and expressed the stem cell-related STAT3 and Bmi1 genes. Interestingly, spheres from both sarcomas remarkably decreased the expression of INK4a/ARF locus genes, p16 INK4a and p19 ARF , which could be related to the resistance against cell senescence and apoptosis. Spheres showed strong tumorigenicity with metastatic potential in vivo via the inoculation into syngeneic rats, suggesting the presence of these populations might contribute to the tumor development such as metastasis via the resistance to apoptotic stimuli.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.08.067