PMID- 11005571 OWN - NLM STAT- MEDLINE DCOM- 20010126 LR - 20190607 IS - 1522-8002 (Print) IS - 1476-5586 (Electronic) IS - 1476-5586 (Linking) VI - 2 IP - 4 DP - 2000 Jul-Aug TI - HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells. PG - 365-77 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 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. FAU - Kaplan, O AU - Kaplan O AD - School of Chemistry, Tel-Aviv University, Ramat Aviv, Israel. FAU - Firon, M AU - Firon M FAU - Vivi, A AU - Vivi A FAU - Navon, G AU - Navon G FAU - Tsarfaty, I AU - Tsarfaty I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Glucosephosphates) RN - 0 (Phospholipids) RN - 0U46U6E8UK (NAD) RN - 53-59-8 (NADP) RN - 67256-21-7 (Hepatocyte Growth Factor) SB - IM MH - Adenocarcinoma MH - Animals MH - Female MH - Glucosephosphates/metabolism MH - Glycolysis/*drug effects MH - Hepatocyte Growth Factor/*pharmacology MH - Mammary Neoplasms, Experimental MH - Mice MH - Models, Biological MH - NAD/metabolism MH - NADP/metabolism MH - Oxidative Phosphorylation/*drug effects MH - Phospholipids/metabolism MH - Signal Transduction MH - Tumor Cells, Cultured PMC - PMC1550289 EDAT- 2000/09/27 11:00 MHDA- 2001/02/28 10:01 PMCR- 2000/07/01 CRDT- 2000/09/27 11:00 PHST- 2000/09/27 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/09/27 11:00 [entrez] PHST- 2000/07/01 00:00 [pmc-release] AID - 0103a [pii] AID - 10.1038/sj.neo.7900103 [doi] PST - ppublish SO - Neoplasia. 2000 Jul-Aug;2(4):365-77. doi: 10.1038/sj.neo.7900103.