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The Journal of Physiological Sciences

, Volume 66, Issue 5, pp 387–396 | Cite as

Inhibition of monocarboxylate transporter 1 suppresses the proliferation of glioblastoma stem cells

  • Tetsuya Takada
  • Kazuyuki Takata
  • Eishi AshiharaEmail author
Original Paper

Abstract

Recent evidence suggests that a minor subset of cancer cells, termed cancer stem cells (CSCs), have self-renewal and tumorigenic potential. Therefore, the characterization of CSCs is important for developing therapeutic strategies against cancer. Cancer cells rely on anaerobic glycolysis to produce ATP even under normoxic conditions, resulting in the generation of excess acidic substances. Cancer cells maintain a weakly alkaline intracellular pH to support functions. Glioblastoma is an aggressive malignancy with a poor 5-year survival rate. Based on the hypothesis that ion transport-related molecules regulate the viability and function of CSCs, we investigated the expression of ion transport-related molecules in glioblastoma CSCs (GSCs). Quantitative RT-PCR analysis showed that monocarboxylate transporter1 (MCT1) were upregulated in GSCs, and inhibition of MCT1 decreased the viability of GSCs compared with that of non-GSCs. Our findings indicate that MCT1 is involved in the maintenance of GSCs and is a promising therapeutic target for glioblastoma.

Keywords

Glioblastoma Cancer stem cell Hypoxia Monocarboxylate transporter Lactic acid Carbonic anhydrase 

Abbreviations

ATP

Adenosine triphosphate

b-FGF

Basic fibroblast growth factor

CA

Carbonic anhydrase

CSC

Cancer stem cell

DMEM

Dulbecco’s modified Eagle’s medium

DMSO

Dimethyl sulfoxide

EGF

Epidermal growth factor

FBS

Fetal bovine serum

GSC

Glioblastoma cancer stem cell

HA

Hypoxia-adapted

MCT

Monocarboxylate transporter

NHE

Na+–H+ exchanger

PC/SM

Penicillin/streptomycin

pHMBS

p-hydroxymercuribenzoic acid sodium salt

qRT-PCR

Quantitative reverse transcription polymerase chain reaction

RT

Room temperature

UPL

Universal probe library

Notes

Acknowledgments

This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (23591404, 26461436 to EA) and a Grant-in-Aid from the Salt Science Research Foundation (1120 to EA).

Compliance with ethical standards

Conflict of interest

T. Takada, K. Takata, and E. Ashihara disclose no financial conflicts of interest.

Supplementary material

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Supplementary material 1 (TIFF 154 kb)
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Supplementary material 2 (TIFF 292 kb)
12576_2016_435_MOESM3_ESM.docx (17 kb)
Supplementary material 3 (DOCX 17 kb)
12576_2016_435_MOESM4_ESM.xlsx (12 kb)
Supplementary material 4 (XLSX 11 kb)

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Copyright information

© The Physiological Society of Japan and Springer Japan 2016

Authors and Affiliations

  • Tetsuya Takada
    • 1
  • Kazuyuki Takata
    • 1
  • Eishi Ashihara
    • 1
    Email author
  1. 1.Department of Clinical and Translational PhysiologyKyoto Pharmaceutical UniversityKyotoJapan

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