Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 2, pp 211–222 | Cite as

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

  • Qin Mao
  • Yu Zhang
  • Xiaoyue Fu
  • Jianxin Xue
  • Wenhao Guo
  • Maobing Meng
  • Zongguang Zhou
  • Xianming Mo
  • You Lu
Original Paper

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.

Keywords

Colon cancer stem cells CD133 Hypoxia Chemotherapeutic resistance 

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • 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
  1. 1.Department of Thoracic Oncology, Cancer CenterWest China Hospital, Sichuan UniversityChengduPeople’s Republic of China
  2. 2.Institute of Digestive SurgeryWest China Hospital, Sichuan UniversityChengduPeople’s Republic of China
  3. 3.Laboratory of Stem Cell BiologyWest China Hospital, Sichuan UniversityChengduPeople’s Republic of China
  4. 4.State Key Laboratory of BiotherapyWest China Hospital, Sichuan UniversityChengduPeople’s Republic of China
  5. 5.Guizhou People’s HospitalGuizhouPeople’s Republic of China

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