Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy.
Addition of choline, ethanolamine, or hemicholinium-3 (a choline kinase inhibitor) to the perfusate of human breast cancer cells monitored by 31P NMR spectroscopy resulted in significant changes to phosphomonoester (PME) and phosphodiester (PDE) signals. These results enable us to assign the PMEs to phosphcholine (PC) and phosphoethanolamine (PE), the PDEs to glycerophosphorylcholine and glycerophosphorylethanolamine, and to define the pathways producing them. The PMEs are products of choline and ethanolamine kinases, the first steps in phospholipid synthesis; and the PDEs are substrates of glycerophosphorylcholine phosphodiesterase, the last step in phospholipid catabolism. Furthermore, PC and PE peaks are twice as intense in cells at log phase versus confluency. We also observed these signals in vivo in human colon and breast tumors grown in mice. Since PMEs are low in most nonproliferating tissues, they could form a basis for noninvasive diagnosis. Also, PE and PC are situated between the control enzymes of two major synthetic pathways and will allow noninvasive 31P NMR studies of these pathways in intact cells and in vivo.
Daly
P F
PF
Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Lyon
R C
RC
Faustino
P J
PJ
Cohen
J S
JS
D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D002794:Choline / Q000494:pharmacology; D019856:Ethanolamine; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006426:Hemicholinium 3 / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010743:Phospholipids / Q000378:metabolism*; D010758:Phosphorus
D004983:Ethanolamines; D010743:Phospholipids; D010758:Phosphorus; D006426:Hemicholinium 3; D019856:Ethanolamine; D002794:Choline