Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NlIR) lias identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phospliocholine-producing enzymes, and uptake of [metliyl- 14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcoholine metabolites contributing to the 1H NMR total clioline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 ± 0.9 and 5.2 ± 2.4 nmol/10 6 cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 ± 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phospliatidylcholine metabolite, whereas average glycerophospliocholine/phosphocholine values decreased significantly to ≤0.2. Two-dimensional {pliosphocholine/total choline, [total choline]} and {glycerophosphocholine/total choline, [total clioline]} maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline Mnase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 ± 0.1 nmol/10 6 cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl- 14C]-choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher (∼ 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phospiiatidylclioline cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvashre clinical tools for EOC diagnosis and treatment follow-up. ©2005 American Association for Cancer Research.
Alterations of choline phospholipid metabolism in ovarian tumor progression / E., Iorio; D., Mezzanzanica; P., Alberti; F., Spadaro; C., Ramoni; S., D'Ascenzo; D., Millimaggi; Pavan, Antonio; V., Dolo; S., Canevari; F., Podo. - In: CANCER RESEARCH. - ISSN 0008-5472. - 65:20(2005), pp. 9369-9376. [10.1158/0008-5472.can-05-1146]
Alterations of choline phospholipid metabolism in ovarian tumor progression
PAVAN, Antonio;
2005
Abstract
Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NlIR) lias identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phospliocholine-producing enzymes, and uptake of [metliyl- 14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcoholine metabolites contributing to the 1H NMR total clioline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 ± 0.9 and 5.2 ± 2.4 nmol/10 6 cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 ± 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phospliatidylcholine metabolite, whereas average glycerophospliocholine/phosphocholine values decreased significantly to ≤0.2. Two-dimensional {pliosphocholine/total choline, [total choline]} and {glycerophosphocholine/total choline, [total clioline]} maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline Mnase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 ± 0.1 nmol/10 6 cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl- 14C]-choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher (∼ 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phospiiatidylclioline cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvashre clinical tools for EOC diagnosis and treatment follow-up. ©2005 American Association for Cancer Research.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
