A factor from pancreatic and colonic cancer cells stimulates glucose uptake and lactate production in myoblasts.
Patients with cancer cachexia exhibit increased glucose flux and lactate production in skeletal muscle. The aim of this study was to examine the direct effect of cancer cell-conditioned media on glucose metabolism in L6 myoblasts. Media from PANC-1 and Colo 320 cells caused a marked time-dependent and concentration-dependent increase of 2-deoxyglucose uptake in GLUT-4 transfected L6 myoblasts. This effect was greater than maximal acute stimulation by insulin and the effect of insulin was additive. Glucose utilization and lactate production increased in parallel to glucose uptake. The effect was inhibited by the protein synthesis inhibitor, cycloheximide and the glucose transport inhibitor, cytochalasin B. The bioactive factor had a molecular weight of approximately 5,000 and the biological activity was destroyed by proteinase K digestion. Radioimmunoassay and immunoneutralization studies indicated the major factor involved is not TNFalpha, IL-1beta, insulin, IGF-I or IGF-II. Further purification and characterization are needed to reveal the identity of this novel factor or factors which may have other metabolic effects that contribute to the cancer cachexia and insulin resistance.
Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska, 68178, USA.
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D000818:Animals; D001685:Biological Factors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019286:Endopeptidase K / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000032:analysis / Q000494:pharmacology; D019344:Lactic Acid / Q000096:biosynthesis*; D008970:Molecular Weight; D015846:Monokines / Q000032:analysis / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051381:Rats; D013002:Somatomedins / Q000032:analysis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001685:Biological Factors; D017077:Culture Media, Conditioned; D051275:Glucose Transporter Type 4; D007328:Insulin; D015846:Monokines; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; C495694:Slc2a4 protein, rat; D013002:Somatomedins; D019344:Lactic Acid; D003571:Cytochalasin B; D003513:Cycloheximide; D003847:Deoxyglucose; D019286:Endopeptidase K; D005947:Glucose