Identification of chemoradiation-resistant osteosarcoma stem cells using an imaging system for proteasome activity

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

doi:10.3892/ijo.2014.2671

December-2014 Volume 45 Issue 6

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December-2014 Volume 45 Issue 6

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Article

Identification of chemoradiation-resistant osteosarcoma stem cells using an imaging system for proteasome activity

Authors:
- Keisuke Tamari
- Kazuhiko Hayashi
- Hideshi Ishii
- Yoshihiro Kano
- Masamitsu Konno
- Koichi Kawamoto
- Naohiro Nishida
- Jun Koseki
- Takahito Fukusumi
- Shinichiro Hasegawa
- Hisataka Ogawa
- Atsushi Hamabe
- Masaaki Miyo
- Kozo Noguchi
- Yuji Seo
- Yuichiro Doki
- Masaki Mori
- Kazuhiko Ogawa
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Affiliations: Department of Radiation Oncology, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan, Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan, Department of Cancer Profiling Discovery, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan, Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, Suita, Osaka 565-0871, Japan
Pages: 2349-2354
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Published online on: September 24, 2014

https://doi.org/10.3892/ijo.2014.2671
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Abstract

Osteosarcoma is the most common primary bone malignancy in pediatric and adolescent populations. Recurrence and metastatic potential can be due to a subpopulation of cells with stem cell-like characteristics, such as tumor-initiating cells (TICs), which maintain the capacity to regenerate entire tumors. Targeting the TICs in osteosarcoma is a promising avenue for the development of new therapies for this devastating disease. TICs are usually quiescent with a low protein turnover, decreased metabolism, and downregulation of proteasome activity. Recently, cancer cells with low proteasome activity have been identified as TICs in several types of cancer. We stably infected two osteosarcoma cell lines, MG-63 and U2-OS, with an expression vector for a fusion protein between the green fluorescent protein, ZsGreen, and the C-terminal degron of the murine ornithine decarboxylase to monitor the 26S proteasome activity in living cells. We separated the osteosarcoma cells with low proteasome activity using fluorescence-activated cell sorting (FACS) and verified whether these ZsGreen+ cells had TIC-like properties. The ZsGreen+ cells showed enhanced sphere formation capacity and underwent asymmetric divisions into ZsGreen+ and ZsGreen- cells, whereas ZsGreen- cells underwent only symmetric divisions into ZsGreen- cells. Moreover, the ZsGreen+ cells were more chemo- and radioresistant. Thus, the present study demonstrated that chemoradiation-resistant TICs can be visualized by this system and suggested the rationale for further study of osteosarcoma stem cells.

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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

Identification of chemoradiation-resistant osteosarcoma stem cells using an imaging system for proteasome activity

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