title: High-capacity glycolytic and mitochondrial oxidative metabolisms mediate the growth ability of glioblastoma.
abstract: Among the primary brain tumors, glioblastoma multiforme (GBM) has a radical proliferation ability that complicates the therapeutic modulation of cancer progression. The majority of GBM patients have a low survival rate (<1 year) due to radical tumor growth and late cancer diagnosis. Previous reports have shown that astrocytes have a specific metabolic organization that includes the production of lactate, the storage of glycogen, and use of lactate to support neurons which possess higher capacity of metabolism compared to neurons. We hypothesized that these characteristics of astrocytes could contribute to enhanced proliferation of GBM compared to neuroblastoma (NB). Here, we show that U87MG cells (a model of GBM) proliferate more rapidly than SH-SY5Y cells (a model of NB). A higher extracellular acidification rate and maximal mitochondrial oxygen consumption rate were observed in U87MG cells compared to SH-SY5Y cells. The expression levels of lactate dehydrogenase (LDH)-A and LDH-B were higher in U87MG cells and primary cultured astrocytes than in SH-SY5Y cells and neurons. Furthermore, the mRNA levels of succinate dehydrogenase and peroxisome proliferator-activated receptor-γ were high in U87MG cells, suggesting that these cells have high capacity for mitochondrial metabolism and uptake of fatty acids related to synthesis of the cell membrane, respectively. Taken together, we demonstrate that GBM cells are characterized by activation of the LDH-expression-related glycolytic pathway and mitochondrial metabolic capacity, suggesting two innate properties of astrocytes that could provide a driving force for the growth ability of GBM. Based on these findings, we propose that therapeutic approaches aimed at treating GBM could target LDH for modulating the metabolic properties of GBM cells.
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Jungim
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Jeongsu
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Yunseon
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Ryu
authors.affiliation: Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 301-747, Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Heo
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006019:Glycolysis; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress