Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells.
CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133(+)) and CD133-negative cells (LC-CD133(-)) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133(+) displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133(+), unlike LC-CD133(-), highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133(+) to form spheres and can further facilitate LC-CD133(+) to differentiate into LC-CD133(-). In addition, knock-down of Oct-4 expression in LC-CD133(+) can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133(+) can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133(+). Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133(+) and malignant lung cancer.
Chen
Yu-Chih
YC
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsu
Han-Shui
HS
Chen
Yi-Wei
YW
Tsai
Tung-Hu
TH
How
Chorng-Kuang
CK
Wang
Chien-Ying
CY
Hung
Shih-Chieh
SC
Chang
Yuh-Lih
YL
Tsai
Ming-Long
ML
Lee
Yi-Yen
YY
Ku
Hung-Hai
HH
Chiou
Shih-Hwa
SH
D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000032:analysis* / Q000276:immunology; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D006023:Glycoproteins; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering