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Virchows Archiv

, Volume 462, Issue 1, pp 83–93 | Cite as

Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma

  • Ai Mogi
  • Kaori Koga
  • Mikiko Aoki
  • Makoto Hamasaki
  • Noriko Uesugi
  • Akinori Iwasaki
  • Takayuki Shirakusa
  • Kazuo Tamura
  • Kazuki NabeshimaEmail author
Original Article

Abstract

Malignant cells supply their energy needs through increased glucose consumption, producing large quantities of lactic acid via glycolysis. Glucose transporters (GLUTs) and monocarboxylate transporters (MCTs) are therefore commonly up-regulated in human malignancies to mediate glucose influx and lactic acid efflux, respectively. However, their roles in malignant pleural mesothelioma (MPM) have not been fully elucidated. Here, we evaluated GLUT-1, MCT-1, and MCT-4 expression in human MPM and reactive mesothelial hyperplasia (RMH) and elucidated their biological role in vitro. GLUT-1, MCT-1, and MCT-4 expression was determined in human MPM (n = 35) and RMH (n = 20) specimens by immunohistochemistry and in frozen tissue, and MPM cell lines, by real-time reverse transcription-polymerase chain reaction and western blot analysis. GLUT-1, MCT-1, and MCT-4 functions in MPM were evaluated by transfection with small interfering RNA. Immunohistochemical analysis revealed higher levels of GLUT-1, MCT-1, and MCT-4 in MPM than in RMH. Additionally, GLUT-1, MCT-1, and MCT-4 mRNA levels were higher in MPM than in non-neoplastic mesothelial cell lines. The siRNA-mediated knockdown of GLUT-1 or MCT-1 significantly suppressed tumor cell proliferation, and MCT-1 silencing inhibited invasion and induced apoptosis. Taken together, these results indicate that combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating MPM from RMH and suggest that MCT-1plays an important biological role.

Keywords

Malignant mesothelioma GLUT-1 MCT-1 MCT-4 

Notes

Acknowledgments

We acknowledge the expert technical assistance of Ms. M. Onitsuka in immunohistochemical and in vitro studies. This work was supported in part by a grant from the Research Center for Advanced Molecular Medicine, Fukuoka University.

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ai Mogi
    • 1
    • 2
  • Kaori Koga
    • 1
  • Mikiko Aoki
    • 1
  • Makoto Hamasaki
    • 1
  • Noriko Uesugi
    • 4
  • Akinori Iwasaki
    • 3
  • Takayuki Shirakusa
    • 5
  • Kazuo Tamura
    • 2
  • Kazuki Nabeshima
    • 1
    Email author
  1. 1.Department of PathologyFukuoka University School of Medicine and HospitalFukuokaJapan
  2. 2.Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious DiseaseFukuoka University School of Medicine and HospitalFukuokaJapan
  3. 3.Thoracic SurgeryFukuoka University School of Medicine and HospitalFukuokaJapan
  4. 4.Department of Pathology, Institute of Basic Medical ScienceGraduate School of Comprehensive Human Sciences, University of TsukubaTsukubaJapan
  5. 5.Department of SurgeryFukusei-Kai HospitalFukuokaJapan

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