Lin Hua, Patel Shaan, Affleck Valerie S, Wilson Ian, Turnbull Douglass M, Joshi Abhijit R, Maxwell Ross, Stoll Elizabeth A
M.Sc. Programme in Medical Sciences, Newcastle University, Newcastle upon Tyne, UK (H.L., V.S.A.); Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK (H.L., V.S.A.); B.Sc. Programme in Physiology, Newcastle University, Newcastle upon Tyne, UK (S.P.); Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK (I.W., R.M.); Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK (D.M.T., E.A.S.); Centre for Brain Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK (D.M.T.); Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK (D.M.T.); Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK (A.R.J.).
M.Sc. Programme in Medical Sciences, Newcastle University, Newcastle upon Tyne, UK (H.L., V.S.A.); Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK (H.L., V.S.A.); B.Sc. Programme in Physiology, Newcastle University, Newcastle upon Tyne, UK (S.P.); Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK (I.W., R.M.); Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK (D.M.T., E.A.S.); Centre for Brain Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK (D.M.T.); Wellcome Trust Centre for Mitochondrial Research, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK (D.M.T.); Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK (A.R.J.)
Neuro Oncol. 2017 Jan;19(1):43-54. doi: 10.1093/neuonc/now128. Epub 2016 Jun 29.
Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per 100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however, the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuel requirements of human glioma cells.
We used database searches and tissue culture resources to evaluate genotype and protein expression, tracked oxygen consumption rates to study metabolic responses to various substrates, performed histochemical techniques and fluorescence-activated cell sorting-based mitotic profiling to study cellular proliferation rates, and employed an animal model of malignant glioma to evaluate a new therapeutic intervention.
We observed the presence of enzymes required for fatty acid oxidation within human glioma tissues. In addition, we demonstrated that this metabolic pathway is a major contributor to aerobic respiration in primary-cultured cells isolated from human glioma and grown under serum-free conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative activity in these primary-cultured cells and prolongs survival in a syngeneic mouse model of malignant glioma.
Fatty acid oxidation enzymes are present and active within glioma tissues. Targeting this metabolic pathway reduces energy production and cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic benefit to patients with malignant glioma. In addition, the expression of fatty acid oxidation enzymes may provide prognostic indicators for clinical practice.
胶质瘤是成人原发性恶性脑肿瘤最常见的形式，每年每10万人中约有4例。与许多肿瘤一样，胶质瘤被认为主要通过糖酵解代谢葡萄糖来产生能量；然而，最近对其对糖酵解的依赖提出了质疑。在本研究中，我们旨在确定人类胶质瘤细胞的代谢燃料需求。
我们利用数据库搜索和组织培养资源来评估基因型和蛋白质表达，跟踪氧气消耗率以研究对各种底物的代谢反应，进行组织化学技术和基于荧光激活细胞分选的有丝分裂分析以研究细胞增殖率，并采用恶性胶质瘤动物模型评估一种新的治疗干预措施。
我们在人类胶质瘤组织中观察到脂肪酸氧化所需酶的存在。此外，我们证明该代谢途径是从人类胶质瘤分离并在无血清条件下培养的原代细胞有氧呼吸的主要贡献者。此外，抑制脂肪酸氧化可降低这些原代培养细胞的增殖活性，并延长恶性胶质瘤同基因小鼠模型的生存期。
脂肪酸氧化酶在胶质瘤组织中存在且具有活性。靶向该代谢途径可减少胶质瘤细胞的能量产生和细胞增殖。药物依托莫昔可能为恶性胶质瘤患者提供治疗益处。此外，脂肪酸氧化酶的表达可为临床实践提供预后指标。
