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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.02.2013 | Original Paper

A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy

verfasst von: Qin Mao, Yu Zhang, Xiaoyue Fu, Jianxin Xue, Wenhao Guo, Maobing Meng, Zongguang Zhou, Xianming Mo, You Lu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2013

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Abstract

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⁻ cells which were also sorted and detected for ki67 and pimonidazole via immunofluorescence.

Results

The hypoxic subpopulation of CD133⁺ and CD133⁻ 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⁻ 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⁻ 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.

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Titel: A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy
verfasst von: Qin Mao
Yu Zhang
Xiaoyue Fu
Jianxin Xue
Wenhao Guo
Maobing Meng
Zongguang Zhou
Xianming Mo
You Lu
Publikationsdatum: 01.02.2013
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-012-1310-3

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A tumor hypoxic niche protects human colon cancer stem cells from chemotherapy