Elsevier

Neoplasia

Volume 2, Issue 4, July–August 2000, Pages 365-377
Neoplasia

HGF/SF Activates Glycolysis and Oxidative Phosphorylation in DA3 Murine Mammary Cancer Cells

https://doi.org/10.1038/sj.neo.7900103Get rights and content
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Abstract

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 MetHGF/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, 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 ymol/hour per milligram protein (P < .05). However, it decreased CO2 levels, 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.

Keywords

HGF/SF
NMR
oxidative phosphorylation
glycolysis

Abbreviations

CLSM
confocal laser scanning microscopy
2-DG
2-deoxyglucose
2DG-6P
2-deoxyglucose-6-phosphate
DMEM
Dulbecco's modified Eagle's medium
DPDE
diphosphodiester
ECL
enhanced chemiluminescence
GPC
glycerophosphocholine
GPE
glycerophosphoethanolamine
HGF/SF
hepatocyte growth factor/scatter factor
NMR
nuclear magnetic resonance
NTP
nucleoside triphosphate
PE
phosphoethanolamine
PC
phosphocholine
PME
phosphomonoester
IP
immunoprecipitation
WB
Western blot analysis
OC
octanoylcamitine
MAL
malate

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