Inhibition of monocarboxylate transporter 1 suppresses the proliferation of glioblastoma stem cells
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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.
KeywordsGlioblastoma Cancer stem cell Hypoxia Monocarboxylate transporter Lactic acid Carbonic anhydrase
Basic fibroblast growth factor
Cancer stem cell
Dulbecco’s modified Eagle’s medium
Epidermal growth factor
Fetal bovine serum
Glioblastoma cancer stem cell
p-hydroxymercuribenzoic acid sodium salt
Quantitative reverse transcription polymerase chain reaction
Universal probe library
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.
- 2.Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J (2003) Identification of a Cancer Stem Cell in Human Brain Tumors. Pathobiology 63:5821–5828Google Scholar
- 18.Hosogi S, Miyazaki H, Nakajima KI, Ashihara E, Niisato N, Kusuzaki K, Marunaka Y (2012) An inhibitor of Na+/H+ exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the cytosolic Cl− concentration via DIDS-sensitive pathways. Cell Physiol Biochem 30:1241–1253CrossRefPubMedGoogle Scholar
- 29.Wilson MC, Meredith D, Fox JEM, Manoharan C, Davies AJ, Halestrap AP (2005) Basigin (CD147) Is the Target for Organomercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4: THE ANCILLARY PROTEIN FOR THE INSENSITIVE MCT2 IS EMBIGIN (gp70). J Biol Chem 280:27213–27221CrossRefPubMedGoogle Scholar
- 36.Miyazaki H, Marunaka Y (2015) The molecular mechanism of intracellular Cl− function in gastric cancer invasion and metastasis by regulating expression of cell adhesion molecules. J Physiol Sci 65(Suppl-1):72Google Scholar
- 37.Miyazaki H, Marunaka Y (2014) Regulatory mechanisms of the G1 to S phase cell cycle progression via changes in the intracellular concentration of Cl− in MKN28 human gastric cancer cells. J Physiol Sci 64(Suppl-1):267Google Scholar
- 38.Hosogi S, Marunaka Y, Niisato N, Kusuzaki K, Miyazaki H (2014) Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell. J Physiol Sci 64(Suppl-1):215Google Scholar