Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines.
The presence of cancer stem cells in both solid and hematopoietic malignancies, has been recently linked to their pathogenesis. Sarcomas are rare, and diversely characterized by degrees of mesenchymal differentiation. The aim of the current study was to demonstrate whether the human sarcoma cell lines, osteosarcoma MG63, Ewing's sarcoma HTB166, fibrosarcoma HT1080, possess the stem-like properties which may contribute to the drug-resistance. All cell lines possessed an ability to form spherical, clonal expanding colonies (sarcospheres) in anchorage-independent, serum-starved conditions. Sarcospheres showed the stem-like properties with the ability of self-renewal, and increased expression of the stem cell-related genes such as Nanog, OCT3/4 SOX2 and DNA repair enzyme genes, MLH1 and MSH2. Sarcospheres showed strong resistance to doxorubicin and cisplatin, and caffeine, a DNA repair inhibitor, enhanced the efficacy of those drugs, suggesting that the drug resistance in sarcosphere cells was partly related to the efficient DNA repair ability. These results indicate that human sarcoma cell lines contain stem-like cell populations with strong drug resistance, and DNA repair inhibitor could enhance the efficacy of chemo-drugs against sarcomas.
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Hiromasa
H
Fujii
Kanya
K
Honoki
Toshifumi
T
Tsujiuchi
Akira
A
Kido
Kazuhiro
K
Yoshitani
Yoshinori
Y
Takakura
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018398:Homeodomain Proteins; C501486:MLH1 protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C527923:SOX10 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D055757:SOXE Transcription Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein