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 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.
Fujii
Hiromasa
H
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Honoki
Kanya
K
Tsujiuchi
Toshifumi
T
Kido
Akira
A
Yoshitani
Kazuhiro
K
Mori
Toshio
T
Takakura
Yoshinori
Y
D000818:Animals; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry* / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D051677:Histiocytoma, Malignant Fibrous / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D050796:STAT3 Transcription Factor; D025803:Tumor Suppressor Protein p14ARF; C508715:p19(ARF) protein, rat