Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells.
Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells.
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DOI：
10.1371/journal.pone.0002637
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发表时间：
2008-07-09
期刊：
影响因子：
3.7
通讯作者：
Chiou, Shih-Hwa
中科院分区：
文献类型：
--
作者：
Chen, Yu-Chih;Hsu, Han-Shui;Chen, Yi-Wei;Tsai, Tung-Hu;How, Chorng-Kuang;Wang, Chien-Ying;Hung, Shih-Chieh;Chang, Yuh-Lih;Tsai, Ming-Long;Lee, Yi-Yen;Ku, Hung-Hai;Chiou, Shih-Hwa
CD 133（CD 133 -1）是一种5-跨膜糖蛋白，近年来被认为是代表肿瘤干细胞样细胞亚群的重要标志物。在此，我们报告了从10名非小细胞肺癌（LC）患者的组织样本和5个LC细胞系中分离出CD 133阳性细胞（LC-CD 133+）和CD 133阴性细胞（LC-CD 133 −）。LC-CD 133+显示出更高的Oct-4表达，具有自我更新的能力，并且可能代表具有产生肺癌细胞的增殖潜力的储库。此外，与LC-CD 133-不同，LC-CD 133+高度共表达多重耐药标志物ABCG 2，并显示出对化疗剂的显著抗性（即，顺铂、依托泊苷、阿霉素和紫杉醇）和放射疗法。用慢病毒载体处理Oct-4 siRNA可以特异性阻断LC-CD 133+形成球体的能力，并可以进一步促进LC-CD 133+分化为LC-CD 133 −。此外，下调LC-CD 133+细胞Oct-4的表达可显著抑制肿瘤的侵袭能力和集落形成能力，并增加caspase 3和聚ADP核糖聚合酶（PARP）的凋亡活性。最后，体外和体内研究进一步证实，Oct-4 siRNA治疗可以提高LC-CD 133+放化疗的治疗效果。总之，我们证明了Oct-4表达在维持LC-CD 133+的自我更新、癌干细胞样和耐化学放射特性中起着至关重要的作用。Oct-4在LC-CD 133+和恶性肺癌中的表达上调值得进一步研究。
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.
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影响因子：
8.4
作者：
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.
通讯作者：
La Porta, Caterina A. M.
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
鉴定非典型畸胎组织/色肽肿瘤中CD133阳性辐射细胞。
影响因子：
3.7
作者：
Chiou, Shih-Hwa;Kao, Chung-Lan;Chen, Yi-Wei;Chien, Chien-Shu;Hung, Shih-Chieh;Lo, Jeng-Fan;Chen, Yann-Jang;Ku, Hung-Hai;Hsu, Ming-Ta;Wong, Tai-Tong
通讯作者：
Wong, Tai-Tong
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ
影响因子：
8
作者：
Monk, M;Holding, C
通讯作者：
Holding, C