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

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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.

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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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Authors and Affiliations

  1. Department of Pathology, Fukuoka University School of Medicine and Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Ai Mogi, Kaori Koga, Mikiko Aoki, Makoto Hamasaki & Kazuki Nabeshima

  2. Department of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University School of Medicine and Hospital, Fukuoka, Japan

    Ai Mogi & Kazuo Tamura

  3. Thoracic Surgery, Fukuoka University School of Medicine and Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Akinori Iwasaki

  4. Department of Pathology, Institute of Basic Medical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki, Tsukuba, 305-8575, Japan

    Noriko Uesugi

  5. Department of Surgery, Fukusei-Kai Hospital, 1-2-36 Noke, Sawara-ku, Fukuoka, 814-0171, Japan

    Takayuki Shirakusa

Authors
  1. Ai Mogi
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  2. Kaori Koga
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  8. Kazuo Tamura
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  9. Kazuki Nabeshima
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Correspondence to Kazuki Nabeshima.

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Mogi, A., Koga, K., Aoki, M. et al. Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma. Virchows Arch 462, 83–93 (2013). https://doi.org/10.1007/s00428-012-1344-6

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  • DOI: https://doi.org/10.1007/s00428-012-1344-6

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