Kaplan O, Firon M, Vivi A, Navon G, Tsarfaty I
School of Chemistry, Tel-Aviv University, Ramat Aviv, Israel.
Neoplasia. 2000 Jul-Aug;2(4):365-77. doi: 10.1038/sj.neo.7900103.
Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth factor which increases cellular motility and has also been implicated in tumor development and progression and in angiogenesis. Little is known about the metabolic alteration induced in cells following Met-HGF/SF signal transduction. The hypothesis that HGF/SF alters the energy metabolism of cancer cells was investigated in perfused DA3 murine mammary cancer cells by nuclear magnetic resonance (NMR) spectroscopy, oxygen and glucose consumption assays and confocal laser scanning microscopy (CLSM). 31P NMR demonstrated that HGF/SF induced remarkable alterations in phospholipid metabolites, and enhanced the rate of glucose phosphorylation (P < .05). 13C NMR measurements, using [13C1]-glucose-enriched medium, showed that HGS/SF reduced the steady state levels of glucose and elevated those of lactate (P < .05). In addition, HGF/SF treatment increased oxygen consumption from 0.58+/-0.02 to 0.71+/-0.03 micromol/hour per milligram protein (P < .05). However, it decreased CO2 levels, and attenuated pH decrease. The mechanisms of these unexpected effects were delineated by CLSM, using NAD(P)H fluorescence measurements, which showed that HGF/SF increased the oxidation of the mitochondrial NAD system. We propose that concomitant with induction of ruffling, HGF/SF enhances both the glycolytic and oxidative phosphorylation pathways of energy production.
肝细胞生长因子/分散因子（HGF/SF）是一种旁分泌生长因子，它可增加细胞运动性，还与肿瘤的发生、发展以及血管生成有关。关于Met-HGF/SF信号转导后细胞内诱导的代谢改变，目前所知甚少。本研究通过核磁共振（NMR）光谱、氧气和葡萄糖消耗测定以及共聚焦激光扫描显微镜（CLSM），在灌注的DA3小鼠乳腺癌细胞中探讨了HGF/SF改变癌细胞能量代谢的假说。31P NMR结果表明，HGF/SF可引起磷脂代谢物的显著变化，并提高葡萄糖磷酸化速率（P <.05）。使用富含[13C1]-葡萄糖的培养基进行的13C NMR测量显示，HGS/SF降低了葡萄糖的稳态水平，提高了乳酸水平（P <.05）。此外，HGF/SF处理使每毫克蛋白质的氧气消耗量从0.58±0.02增加至0.71±0.03微摩尔/小时（P <.05）。然而，它降低了二氧化碳水平，并减弱了pH值的下降。通过CLSM利用NAD(P)H荧光测量对这些意外效应的机制进行了阐述，结果表明HGF/SF增加了线粒体NAD系统的氧化作用。我们认为，伴随着褶皱的诱导，HGF/SF增强了能量产生的糖酵解和氧化磷酸化途径。
