Characterization of a specific signal from human pancreatic tumors heterotransplanted into nude mice. Study by high resolution 1H NMR and HPLC.
In a previous study, we demonstrated the existence of a 3.2 +/- 0.2 ppm peak in the 1H NMR spectrum at 60 MHz from human pancreatic adenocarcinomas (Capan-1 cell) heterotransplanted into nude mice. This peak, which is not present in normal human pancreas, was attributed to enhanced membrane fluidity and/or or an increase in phospholipid turnover. The present study was designed to identify this signal by comparing the 1H NMR spectra recorded in vivo at 100 MHz from Capan-1 tumors, after suppression of the tissular water proton peak, to those recorded from normal pancreatic tissue, and to those recorded at 300 MHz from lipid extracts. The 1H NMR spectra at 100 MHz of the Capan-1 tumors in vivo exhibited three main peaks in the 3.2 +/- 0.2 ppm region: 1. A peak at 2.8 +/- 0.1 ppm from CH2 protons of the acyl chains of unsaturated phospholipids; 2. A peak at 3.2 +/- 0.1 ppm from the protons of the N(CH3)3 group of choline; and 3 A peak at 3.5 +/- 0.1 ppm attributed to GPC. The NMR 1H 300 MHz spectrum of phospholipid extracts of Capan-1 tumors displayed 12 principal resonances, of which only the N(CH3)3 peak of PC had a similar chemical shift to that observed at low resolution (3.2 +/- 0.2 ppm). This peak had a higher intensity in the xenografts than in normal human pancreatic tissue. HPLC analysis of the same lipid extracts from Capan-1 cells in culture, of tumors derived from these cells and from normal pancreas showed: 1. Identical concentrations of the different phospholipids from cancerous human pancreatic cells in vivo and in culture; and 2. A significantly higher level of PC in the extracts of normal human pancreatic tissue. The increase in intensity of the N(CH3)3 peak of PC in the Capan-1 tumors was not thought to be caused by an increase in PC concentration, but to a difference in conformation or mobility of the PC protons in the xenografts. The increase in relaxation time in cancerous tissue (from 60 to 125 ms) was also taken to be evidence in favor of a high mobility of protons.(ABSTRACT TRUNCATED AT 400 WORDS)
Laboratoire de Biologie Cellulaire, Universite Paul Sabatier, Toulouse, France.
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Chemin-Thomas
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Esclassan
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Palevody
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Hollande
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D014183:Transplantation, Heterologous
D010713:Phosphatidylcholines; D010743:Phospholipids