title: Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma.
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.
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine and Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Mogi
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Mikiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Uesugi
authors.forename: Akinori
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shirakusa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nabeshima
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D004848:Epithelium / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D051272:Glucose Transporter Type 1; C115081:MCTS1 protein, human; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; C406962:SLC16A4 protein, human