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

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.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Lee YH,Yang HW,Yang LC,Lu MY,Tsai LL,Yang SF,Huang YF,Chou MY,Yu CC,Hu FW

doi

10.3892/ol.2017.6132

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

171-179

issue

1

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-6132

journal_volume

14

pub_type

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