Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells

Yu Chih Chen*, Han Shui Hsu, Yi Wei Chen, Tung Hu Tsai, Chorng Kuang How, Chien Ying Wang, Shih Chieh Hung, Yuh Lih Chang, Ming Long Tsai, Yi Yen Lee, Hung Hai Ku, Shih Hwa Chiou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

449 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere2637
JournalPLoS ONE
Volume3
Issue number7
DOIs
StatePublished - 9 Jul 2008

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