Visualization and characterization of cancer stem-like cells in cervical cancer

Hayashi,Kazuhiko; Tamari,Keisuke; Ishii,Hideshi; Konno,Masamitsu; Nishida,Naohiro; Kawamoto,Koichi; Koseki,Jun; Fukusumi,Takahito; Kano,Yoshihiro; Nishikawa,Shimpei; Miyo,Masaaki; Noguchi,Kozo; Ogawa,Hisataka; Hamabe,Atsushi; Seo,Yuji; Doki,Yuichiro; Mori,Masaki; Ogawa,Kazuhiko

doi:10.3892/ijo.2014.2670

December-2014 Volume 45 Issue 6

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December-2014 Volume 45 Issue 6

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Article

Visualization and characterization of cancer stem-like cells in cervical cancer

Authors:
- Kazuhiko Hayashi
- Keisuke Tamari
- Hideshi Ishii
- Masamitsu Konno
- Naohiro Nishida
- Koichi Kawamoto
- Jun Koseki
- Takahito Fukusumi
- Yoshihiro Kano
- Shimpei Nishikawa
- Masaaki Miyo
- Kozo Noguchi
- Hisataka Ogawa
- Atsushi Hamabe
- Yuji Seo
- Yuichiro Doki
- Masaki Mori
- Kazuhiko Ogawa
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Affiliations: Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
Pages: 2468-2474
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Published online on: September 24, 2014

https://doi.org/10.3892/ijo.2014.2670
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Abstract

Cancer stem cells (CSCs), defined by their differentiation capacity, self-renewal capacity, and maintenance of proliferation, have been identified in many tumors, including cervical cancer. Current studies identify CSCs by several specific biomarkers; however, it is difficult to monitor cervical CSCs in real-time in vitro and in vivo. Recent research reported the visualization of CSCs in breast cancer and gliomas using green fluorescent protein, ZsGreen, fused to a degron motif ornithine decarboxylase (ODC), which is destroyed by proteasomes. Accordingly, CSCs have low 26S proteasome activity, whereas non-CSCs have high 26S proteasome activity. Therefore, it is possible to observe CSCs by their accumulation of the fluorescent ZsGreen protein. In this study, we investigated optical imaging parameters to evaluate CSCs using two human cervical cancer cell lines: CaSki and HeLa. We defined populations as cell types having high- and low ZsGreen-cODC (high- and low-Zs, respectively) expression levels. The results of a sphere-forming assay revealed that the self-renewal ability of the high-Zs population was significantly higher than that of the low-Zs population. A tumorigenicity assay confirmed that the high-Zs population exhibited higher tumorigenic potential than the low-Zs population. The radioresistance of the high-Zs population of both HeLa and CaSki cells and the chemoresistance of the high-Zs population of CaSki cells were confirmed by a clonogenic survival assay and the tetrazolium dye assay, respectively. These results indicate that high-Zs populations of both the HeLa and CaSki cell lines possess CSC-like properties and therapeutic resistance. In conclusion, we successfully visualized CSC-like cells using a fluorescent protein system.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Visualization and characterization of cancer stem-like cells in cervical cancer

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Abstract

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