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90007563

publisher

Acquisition of cancer stem cell properties in osteosarcoma cells by defined factors

/ A1442 / / / A1471 / / / / A1461 / A1443 / A1438 / A1418 / A0443 / A0444 / A0783 / A0784

Fujiwara, Shuichi
Kawamoto, Teruya
Kawakami, Yohei
Koterazawa, Yasufumi
Hara, Hitomi
Takemori, Toshiyuki
Kitayama, Kazumichi
Yahiro, Shunsuke
Kakutani, Kenichiro
Matsumoto, Tomoyuki
Matsushita, Takehiko
Niikura, Takahiro
Koyanagi-Aoi, Michiyo
Aoi, Takashi
Kuroda, Ryosuke
Akisue, Toshihiro

/ 河本, 旭哉 / / / 原, 仁美 / / / / 角谷, 賢一朗 / 松本, 知之 / 松下, 雄彦 / 新倉, 隆宏 / 青井, 三千代 / 青井, 貴之 / 黒田, 良祐 / 秋末, 敏宏

11(1)

429

BMC

2020-10-02

© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

2020-10-26

17576512

eng

/ 1000030420558 / / / 1000040437489 / / / / 1000010533739 / 1000050546588 / 1000040467650 / 1000040448171 / 1000090432327 / 1000000546997 / 1000080379362 / 1000090379363

Background Cancer stem cells (CSCs) are considered to be responsible for tumor initiation, formation, and poor prognosis of cancer patients. However, the rarity of CSCs in clinical samples makes it difficult to elucidate characteristics of CSCs, especially in osteosarcoma (OS). The aim of this study is to verify whether it is possible to generate CSC-like cells by transducing defined factors into an OS cell line. Methods We retrovirally transduced the Octamer-binding transcription factor 3/4 (OCT3/4), Kruppel-like factor 4 (KLF4), and SRY-box transcription factor 2 (SOX2) genes into the MG-63 human OS cell line (MG-OKS). Parental and GFP-transduced MG-63 cells were used as negative control. We assessed the properties of the generated cells in vitro and in vivo. Multiple comparisons among groups were made using a one-way analysis of variance (ANOVA) followed by post hoc testing with Tukey's procedure. Results MG-OKS cells in vitro exhibited the significantly increased mRNA expression levels of CSC markers (CD24, CD26, and CD133), decreased cell growth, increased chemoresistance and cell migration, and enhanced sphere formation. Notably, MG-OKS cells cultured under osteogenic differentiation conditions showed strongly positive staining for both Alizarin Red S and alkaline phosphatase, indicating osteogenesis of the cells. Gene ontology analysis of microarray data revealed significant upregulation of epidermal-related genes. Tumors derived from MG-OKS cells in vivo were significantly larger than those from other cells in μCT analysis, and immunohistochemical staining showed that Ki-67, osteocalcin, and HIF-1α-positive cells were more frequently detected in the MG-OKS-derived tumors. Conclusions In this study, we successfully generated OS CSC-like cells with significantly enhanced CSC properties following transduction of defined factors.

Cancer stem cells / Chemoresistance / Osteosarcoma / Sarcosphere / Tumorigenicity

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2020-10-26