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

Our plain-English summary of Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma, by A. Mogi, K. Koga, M. Aoki, et al (Virchows Archiv, 2013).

The study

• Authors: A. Mogi, K. Koga, M. Aoki, M. Hamasaki, N. Uesugi, A. Iwasaki, T. Shirakusa, K. Tamura, K. Nabeshima
• Journal: Virchows Archiv
• Published: 2013;462(1):83-93
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This laboratory study from Fukuoka, Japan, looked at three proteins in malignant pleural mesothelioma. GLUT-1 helps cells take up glucose; MCT-1 and MCT-4 help cells export lactic acid. The authors stained tissue from 35 mesothelioma cases and from 20 cases of reactive mesothelial hyperplasia, a non-cancerous condition. All cases were diagnosed between 1980 and 2009. GLUT-1 staining was positive in 20 of 35 mesotheliomas and in none of the hyperplasia samples. High MCT-1 staining was seen in 28 of 35 mesotheliomas and 3 of 20 hyperplasia samples. High MCT-4 staining was seen in 22 of 35 and 4 of 20. In mesothelioma cells grown in the laboratory, lowering each protein with small interfering RNA significantly slowed cell growth. Lowering MCT-1 also raised a marker of programmed cell death and reduced the cells' ability to invade, while the effects of lowering GLUT-1 or MCT-4 on invasion were not statistically significant. The authors concluded that combining the three stains might help tell mesothelioma apart from reactive hyperplasia. They noted that GLUT-1 alone detected only 57% of the mesotheliomas. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study: immunohistochemical staining of archived human tissue, plus in vitro experiments on cell lines using small interfering RNA (siRNA) to reduce each protein
• Who was studied: 35 cases of malignant pleural mesothelioma (MPM) and 20 cases of reactive mesothelial hyperplasia (RMH), diagnosed 1980 to 2009 at Fukuoka University Hospital and Kyushu Medical Center, Japan. The mesotheliomas were 23 epithelioid, 4 sarcomatoid, 7 biphasic and 1 lymphohistiocytoid. The laboratory work used four MPM cell lines (ACC-MESO-1, CRL-5946, CRL-5915, CRL-2081) and one non-neoplastic mesothelial cell line (Met-5A).
• Exposure: Not an exposure study. The article does not report the patients' asbestos exposure. It measured expression of GLUT-1, MCT-1 and MCT-4.
• Main results:
  • GLUT-1 was positive in 57% (20/35) of MPM specimens (15% diffusely, the rest focally) and in none of the RMH specimens.
  • High MCT-1 staining scores were found in 80% (28/35) of MPM specimens and 15% (3/20) of RMH specimens.
  • High MCT-4 staining scores were found in 63% (22/35) of MPM specimens and 20% (4/20) of RMH specimens.
  • Three of the four MPM cell lines had higher GLUT-1, MCT-1 and MCT-4 mRNA levels than the non-neoplastic Met-5A cells.
  • At the protein level, Met-5A cells had more GLUT-1 than three of the four MPM cell lines.
  • In CRL-5915 cells, siRNA reduced GLUT-1 by 25%, MCT-1 by 50% and MCT-4 by 43% compared with controls.
  • In CRL-5915 cells, siRNA against GLUT-1, MCT-1 or MCT-4 significantly inhibited proliferation. The effect was weaker with MCT-4 siRNA.
  • MCT-1 siRNA raised caspase-3/7 activity, a marker of programmed cell death, compared with controls. GLUT-1 and MCT-4 siRNAs did not.
  • In CRL-5915 cells, MCT-1 siRNA blocked invasion at 48 hours. GLUT-1 and MCT-4 siRNAs did not significantly inhibit invasion.
• The authors' conclusion: The authors concluded that combining GLUT-1 and MCT-1/MCT-4 immunostaining might improve the ability to distinguish MPM from RMH.
• Limitations the authors state:
  • The authors noted that GLUT-1 staining had low sensitivity (57%) in their study. They suggested that small biopsies may have contained only GLUT-1-negative parts of tumors.
  • mRNA and protein could not be measured in the reactive (non-neoplastic) mesothelial tissue because the samples were too small.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Reactive Mesothelial Hyperplasia, Immunohistochemistry, Mesothelial Cells, Apoptosis.

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