A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy
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- 作者：Qin Mao (1) (4)
Yu Zhang (1) (4) (5)
Xiaoyue Fu (1) (4)
Jianxin Xue (1) (4)
Wenhao Guo (1) (4)
Maobing Meng (1) (4)
Zongguang Zhou (2)
Xianming Mo (3)
You Lu (1) (4) - 关键词：Colon cancer stem cells ; CD133 ; Hypoxia ; Chemotherapeutic resistance
- 刊名：Journal of Cancer Research and Clinical Oncology
- 出版年：2013
- 出版时间：February 2013
- 年：2013
- 卷：139
- 期：2
- 页码：211-222
- 全文大小：1022KB
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Yu Zhang (1) (4) (5)
Xiaoyue Fu (1) (4)
Jianxin Xue (1) (4)
Wenhao Guo (1) (4)
Maobing Meng (1) (4)
Zongguang Zhou (2)
Xianming Mo (3)
You Lu (1) (4)
1. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China
4. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
5. Guizhou People’s Hospital, Guizhou, People’s Republic of China
2. Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
3. Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China - ISSN：1432-1335
文摘
Purpose Hypoxia has been found to play an important role in regulating the biological characteristics of cancer stem cells (cCSCs). In this study, we tested whether a tumor hypoxic niche serves to the chemotherapeutic resistance of colon cCSCs. Methods Each of 23 fresh samples of human colon adenocarcinoma was transplanted into nude mice. The tumor-bearing mice randomly and equally received (A) saline, (B) 5-fluorouracil (15?mg/kg), (C) oxaliplatin (10?mg/kg), and (D) oxaliplatin plus 5-fluorouracil when xenografts reached 250?mm3 (n?=?10). After 2-week treatment, tumor cells were quantified by flow cytometry for expression of CD133 and the hypoxic proportion of CD133+ and CD133?/sup> cells which were also sorted and detected for ki67 and pimonidazole via immunofluorescence. Results The hypoxic subpopulation of CD133+ and CD133?/sup> cells was 66.5 and 26.4?%, respectively. Although there was no marked change for the hypoxic subpopulation of CD133+ cells after treatment, the hypoxic fraction of proliferative CD133+ cells was increased by 14.62, 16.45, and 20.46?% in groups B, C, and D, respectively. Furthermore, proliferative cells in CD133+ and CD133?/sup> cells were reduced by 29.93 and 62.5?% in group C, and by 25.26 and 68.22?% in group D; in group B, however, the proliferative CD133+ cells were increased by 37.09?%; the CD133?/sup> cells were unchanged. Conclusions Most CD133+ cCSCs are located in a hypoxic niche, where cCSCs are better at retaining proliferating property under chemotherapy. Oxaliplatin, rather than 5-FU, inhibits proliferation of cCSCs, which may be the mechanism underlying a better outcome by oxaliplatin in colon cancer patients.