Open Access

DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells

  • Authors:
    • Yu‑Hsien Lee
    • Hui‑Wen Yang
    • Li‑Chiu Yang
    • Ming‑Yi Lu
    • Lo‑Lin Tsai
    • Shun‑Fa Yang
    • Yu‑Feng Huang
    • Ming‑Yung Chou
    • Cheng‑Chia Yu
    • Fang‑Wei Hu
  • View Affiliations

  • Published online on: May 8, 2017     https://doi.org/10.3892/ol.2017.6132
  • Pages: 171-179
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor-initiating cells (TICs) are defined as a specialized subset of cells with tumor-initiating capacity that can initiate tumor growth, tumor relapse and metastasis. In the present study, osteosarcoma TICs (OS‑TICs) were isolated and enriched from the osteosarcoma U2OS and MG‑63 cell lines using sphere formation assays and serum‑depleted media. These enriched OS-TICs showed the expression of several typical cancer stemness markers, including octamer‑binding transcription factor 4, Nanog homeobox, cluster of differentiation (CD)117, Nestin and CD133, and the expression of ATP binding cassette subfamily G member 2, multidrug resistance protein 1 (MDR1) and dihydrofolate reductase (DHFR). Notably, in vitro and in vivo tumorigenic properties were enhanced in these OS‑TICs. Additionally, methotrexate and doxorubicin are the most widely used anticancer agents against osteosarcoma, and the observed enhanced chemoresistance of OS‑TICs to these two agents could be associated with the upregulation of DHFR and MDR1. These findings suggest that the upregulation of DHFR and MDR1 is associated with the development of chemoresistance of OS‑TICs.
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July-2017
Volume 14 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Lee YH, Yang HW, Yang LC, Lu MY, Tsai LL, Yang SF, Huang YF, Chou MY, Yu CC, Hu FW, Hu FW, et al: DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells. Oncol Lett 14: 171-179, 2017.
APA
Lee, Y., Yang, H., Yang, L., Lu, M., Tsai, L., Yang, S. ... Hu, F. (2017). DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells. Oncology Letters, 14, 171-179. https://doi.org/10.3892/ol.2017.6132
MLA
Lee, Y., Yang, H., Yang, L., Lu, M., Tsai, L., Yang, S., Huang, Y., Chou, M., Yu, C., Hu, F."DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells". Oncology Letters 14.1 (2017): 171-179.
Chicago
Lee, Y., Yang, H., Yang, L., Lu, M., Tsai, L., Yang, S., Huang, Y., Chou, M., Yu, C., Hu, F."DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells". Oncology Letters 14, no. 1 (2017): 171-179. https://doi.org/10.3892/ol.2017.6132