HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells

Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth fact or 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 transduct ion. The hypothesis that HGF/SF alters the energy metabolism of cancer cell s was investigated in perfused DA3 murine mammary cancer cells by nuclear m agnetic resonance (NMR) spectroscopy, oxygen and glucose consumption assays and confocal laser scanning microscopy (CLSM), P-31 NMR demonstrated that HGF/SF induced remarkable alterations in phospholipid metabolites, and enha nced the rate of glucose phosphorylation (P < .05). C-13 NMR measurements, using [C-13(1)]-glucose-enriched medium, showed that HGS/SF reduced the ste ady state levels of glucose and elevated those of lactate (P < ,05), In add ition, HGF/SF treatment increased oxygen consumption from 0.58 +/- 0.02 to 0.71 +/- 0.03 mu mol/hour per milligram protein (P < .05), However, it decr eased CO2 levels, and attenuated pH decrease. The mechanisms of these unexp ected effects were delineated by CLSM, using NAD(P)H fluorescence measureme nts, 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 ener gy production.