Establishment of a human colorectal cancer cell line P6C with stem cell properties and resistance to chemotherapeutic drugs.
Establishment of a human colorectal cancer cell line P6C with stem cell properties and resistance to chemotherapeutic drugs.
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具有干细胞特性和化疗药物抗性的人结直肠癌细胞系P6C的建立
DOI：
10.1038/aps.2013.56
复制
发表时间：
2013-06
影响因子：
8.2
通讯作者：
Chen, Quan
中科院分区：
文献类型：
--
作者：
Rao, Guan-hua;Liu, Hong-min;Li, Bao-wei;Hao, Jia-jie;Yang, Yan-lei;Wang, Ming-rong;Wang, Xiao-hui;Wang, Jun;Jin, Hai-jing;Du, Lei;Chen, Quan
关键词：
目的：肿瘤干细胞具有启动和维持肿瘤生长的能力。在本研究中，我们建立了CD44+结直肠癌干细胞系，重点研究了其自我更新能力、增强的肿瘤起始性和耐药性。方法：收集13例手术前未接受化疗或放疗的新鲜结肠癌和配对的正常结肠癌组织。在6个单细胞来源的克隆中，只有P6C细胞系连续培养20代以上，形成高效的全克隆，然后检测P6C细胞系的干性基因表达、集落形成、致瘤性和药物敏感性。结果：P6C细胞系表达干性蛋白，包括c-Myc、Oct3/4、Nanog、Lgr5和SOX2。Oct3/4阳性的P6C细胞主要通过对称分裂产生全克隆，少数P6C细胞通过不对称分裂产生分体克隆。P6C细胞稳定表达CD44，具有较强的形成肿瘤球体的能力。单个细胞衍生的球体能够在裸鼠体内产生异种移植瘤。与SW480和HCT116细胞相比，P6C细胞对治疗结直肠癌常用的化疗药物喜树碱和5-氟尿嘧啶具有高度的耐药性。结论：我们建立了一株具有正常干细胞特性的高致瘤能力的结直肠癌干细胞株P6C。这将有助于癌症干细胞的机制研究和针对癌症干细胞的药物的开发。
Aim:Cancer stem cells have the capacity to initiate and sustain tumor growth. In this study, we established a CD44+ colorectal cancer stem cell line with particular emphasis on its self-renewal capacity, enhanced tumor initiation and drug resistance.Methods:Fresh colon cancer and paired normal colon tissues were collected from 13 patients who had not received chemotherapy or radiotherapy prior to surgery. Among the 6 single-cell derived clones, only the P6C cell line was cultured for more than 20 passages in serial culture and formed holoclones with high efficiency, and then the stemness gene expression, colony formation, tumorigenicity and drug sensitivities of the P6C cell line were examined.Results:Stemness proteins, including c-Myc, Oct3/4, Nanog, Lgr5, and SOX2, were highly expressed in the P6C cell line. Oct3/4-positive P6C cells mostly generated holoclones through symmetric division, while a small number of P6C cells generated meroclones through asymmetric division. P6C cells stably expressed CD44 and possessed a high capacity to form tumor spheres. A single cell-derived sphere was capable of generating xenograft tumors in nude mice. Compared to SW480 and HCT116 colorectal cancer cells, P6C cells were highly resistant to Camptothecin and 5-fluorouracil, the commonly used chemotherapeutic agents to treat colorectal cancers.Conclusion:We established a colorectal cancer stem cell line P6C with a high tumorigenic capacity and the characteristics of normal stem cells. It will benefit the mechanistic studies on cancer stem cells and the development of drugs that specifically target the cancer stem cells.
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影响因子：
56.9
作者：
Schepers, Arnout G.;Snippert, Hugo J.;Clevers, Hans
通讯作者：
Clevers, Hans
DOI：
10.1385/scr:1:3:207
发表时间：
2005-01-01
期刊：
STEM CELL REVIEWS
影响因子：
--
作者：
Dontu, Gabriela;Liu, Suling;Wicha, Max S.
通讯作者：
Wicha, Max S.
影响因子：
25
作者：
Bylund, M;Andersson, E;Muhr, J
通讯作者：
Muhr, J
影响因子：
64.5
作者：
Hochedlinger, K;Yamada, Y;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
6.7
作者：
Boman, B. M.;Wicha, M. S.;Runquist, O. A.
通讯作者：
Runquist, O. A.