TY - JOUR
T1 - HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells
AU - Kaplan, Ofer
AU - Firon, Michal
AU - Vivi, Antonio
AU - Navon, Gil
AU - Tsarfaty, Han
N1 - Funding Information:
Partially supported by a grant from the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities. We thank Leonid Mittelman (Interd epart-mental Core Facility, Sackler School of Medicine, Tel-Aviv University) for his excellent assistance with confocal microscopy. We thank Miriam Shaharabany and Mr. Rom T. Altstock for critical review of this work.
PY - 2000
Y1 - 2000
N2 - 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 μmol/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.
AB - 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 μmol/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.
KW - Glycolysis
KW - HGF/SF
KW - NMR
KW - Oxidative phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=0033813154&partnerID=8YFLogxK
U2 - 10.1038/sj.neo.7900103
DO - 10.1038/sj.neo.7900103
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AN - SCOPUS:0033813154
SN - 1522-8002
VL - 2
SP - 365
EP - 377
JO - Neoplasia
JF - Neoplasia
IS - 4
ER -
