Phospholipid profiles of human colon cancer using 31P magnetic resonance spectroscopy

  • T. E. Merchant
  • J. N. Kasimos
  • P. W. de Graaf
  • B. D. Minsky
  • L. W. Gierke
  • T. Glonek
Original Articles
Accepted:

Abstract

Phospholipids of 16 malignant and 11 non-malignant human colon specimens were analyzed using a chloroform-methanol analytical reagent in conjunction with 31P magnetic resonance spectroscopy (MRS) at 202.4 MHz. Sixteen individual generic phospholipids were identified and quantified for statistical intergroup comparisons. Statistically significant elevations in the relative concentrations of lysophosphatidylcholine and phosphatidylcholine plasmalogen were seen in malignant tissues along with significantly depressed levels of sphingomyelin and phosphatidylethanolamine plasmalogen. The malignant and non-malignant tissue groups were further differentiated by the detection of the minor phospholipids, lysophosphatidylcholine plasmalogen, lysophosphatidylethanolamine plasmalogen, lysophosphatidic acid and phosphatidylglycerol exclusively present in the malignant tissues and by significant changes in computed phospholipid metabolic indices that were dominated by choline containing lipids. The 31P MRS methods used represent an advancement over previous protocols for identifying and quantifying major and minor tissue phospholipids making this the first direct study of membrane phospholipids in human colon tissues using 31P MRS. The phospholipid profiles obtained may provide important information regarding the nature of the malignant cell's membrane system and identify markers which may be used to estimate malignant propensity, aggressiveness of disease and provide prognostic information.

Keywords

Magnetic Resonance Spectroscopy Human Colon Malignant Tissue Lysophosphatidic Acid Tissue Phospholipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Les phospholipides de 16 échantillons de colons humains atteints de tumeurs malignes de 11 sans tumeur maligne ont été analysés en utilisant une méthode analytique avec un réactif chloroforme-métanol en conjonction avec une résonance magnétique spectroscopique (MRS au P31 à 202,4 MHz). 16 phospholipides différents ont été identifiés et quantifiés pour des comparaisons statistiques inter-groupes. Une élèvation statistiquement significative dans les concentrations relatives de l'isophosphatidylcholine et phosphatidylcholine plasmalogène ont été trouvées dans le tissue malin avec des taux significativement diminués de sphingomyéline et de phosphatidylétanolamine plasmalogène. Les groupes de tissus malins et non malins ont été de plus différenciés par la détection des phospholipides mineurs, lysophosphatidylcholine plasmalogène, lyophosphatidylétanolamine plasmalogène, acide lysophasphatidique et phosphatidylglycérol exclusivement présents dans les tissus malins ainsi que par des différences significatives des indices métaboliques computérisés de phospholipides qui étaient dominés par des lipides contenant de la choline. La résonance magnétique par spectroscopie au P31 utilisée représente une avance sur tous les protocoles précedents pour identifier et quantifier les phospholipides tissulaires majeurs et mineurs faisant de cette méthode la première étude directe des phospholipides membranaires du colon humain utilisant la résonance magnétique par spectroscopie au P31. Le profil de phospholipides obtenu peut fournir des informations importantes quant à la nature du système menbranaire des cellules malignes et identifier des marqueurs qui pourraient être utilisés pour estimer le potentiel malin, l'agressivité de la maladie et fournir des informations pronostiques.

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References

  1. 1.
    Winawer SJ, Flehinger BJ, Buchalter J, Herbert E, Shike M (1990) Declining serum cholesterol levels prior to diagnosis of colon cancer. JAMA 263:2083–2085Google Scholar
  2. 2.
    Kostic N, Bozanic M, Cvetkovic R (1989) Serum cholesterol and triglycerides in patients with benign and malignant tumors of the colon and rectum. Srp Arh Celok Lek 117:325–334Google Scholar
  3. 3.
    Robblee NM, Farnworth ER, Bird RP (1988) Phospholipid profile and production of prostanoids by murine colonic epithelium: Effect of dietary fat. Lipids 23:334–339Google Scholar
  4. 4.
    Bull AW, Soullier BK, Wilson PS, Hayden MT, Nigro ND (1979) Promotion of Azoxymethane-induced intestinal cancer by high fat diet in rats. Cancer Res 39:4956–4959Google Scholar
  5. 5.
    Sakaguchi M, Minoura T, Hiramatsu Y, Takada-H, Yamamura M, Hioki K, Yamamoto M (1986) Effects of dietary saturated and unsaturated fatty acids on fecal bile acids and colon carcinogenesis induced by azoxymethane in rats. Cancer Res 46:61–65Google Scholar
  6. 6.
    Brasitus TA, Dudeja PK, Dahiya R (1986) Premalignant alterations in lipid composition and fluidity of colonic brush border membranes of rats administered 1,2-dimethylhyrazine. J Clin Invest 77:831–840Google Scholar
  7. 7.
    Brasitus TA, Dudeja PK, Dahiya R, Brown MD (1987) 1,2-Dimethylhydrazine-induced alterations in colonic plasma membrane fluidity: restriction to the luminal region. Biochim Biophys Acta 896:311–317Google Scholar
  8. 8.
    Halline AG, Dudeja PK, Brasitus TA (1988) 1,2-Dimethylhydrazine-induced premalignant alterations in the S-adenosylmethionine/S-adenosylhomocysteine ratio and membrane lipid lateral diffusion of the rat distal colon. Biochim Biophys Acta 944:101–107Google Scholar
  9. 9.
    Dudeja PK, Dahiya R, Brasitus TA (1986) The role of sphingomyelin synthetase and sphingomyelinase in 1,2-dimethylhydrazine-induced lipid alterations of rat colonic plasma membranes. Biochim Biophys Acta 863:309–312Google Scholar
  10. 10.
    Meneses P, Glonek T (1988) High resolution 31P NMR of extracted phospholipids. J Lipid Res 29:679–689Google Scholar
  11. 11.
    Kasimos JN, Merchant TE, Gierke LW, Glonek T (1990) 31P magnetic resonance spectroscopy of human colon cancer. Cancer Res 50:527–532Google Scholar
  12. 12.
    Masella R, Cantafora A, Guidoni L, Luciani AM, Mariutti G, Rosi A, Viti V (1989) Characterization of vesicles, containing an acylated oligopeptide, released by human colon adenocarcinoma cells. NMR and biochemical studies. FEBS Lett 246:25–29Google Scholar
  13. 13.
    Guidoni L, Mariutti G, Rampelli GM, Rosi A, Viti V (1987) Mobile phospholipid signals in NMR spectra of cultured human adenocarcinoma cells. Magn Reson Med 5:578–585Google Scholar
  14. 14.
    Daly PF, Lyon RC, Faustino PJ, Cohen JS (1987) Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy. J Biol Chem 262:1487–1488Google Scholar
  15. 15.
    Rosi A, Guidoni L, Luciani AM, Mariutti G, Viti V (1988) RNA-lipid complexes released from the plasma membrane of human colon carcinoma cells. Cancer Lett 39:153–160Google Scholar
  16. 16.
    Meneses P, Para PF, Glonek T (1989) 31P NMR of tissue phospholipids: A comparison of three tissue pre-treatment procedures. J Lipid Res 30:458–461Google Scholar
  17. 17.
    Folch J, Lees M, Sloan-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509Google Scholar
  18. 18.
    Glonek T, Van Wazer JR (1974) Aqueous tetrahydrophosphonium perchlorate as a narrow-line 31P NMR reference substance. J Magn Reson 13:390–391Google Scholar
  19. 19.
    Greiner JV, Kopp SJ, Sanders DR, Glonek T (1981) Organophosphates of the crystalline lens. A nuclear magnetic resonance spectroscopic study. Invest Ophthalmol Vis Sci 21:700–713Google Scholar
  20. 20.
    Barany M, Glonek T (1982) Phosphorus-31 nuclear magnetic resonance of contractile systems. In: Fredericksen DL, Cunningham LW (eds) Methods in enzymology, vol 85B. Academic Press, New York, pp 624–676Google Scholar
  21. 21.
    Kirkpatrick DS, Bishop SH (1971) Simplified wet ash procedure for total phosphorus analysis of organophosphates in biological samples. Anal Chem 43:1707–1709Google Scholar
  22. 22.
    Semble EL, Wu WC (1989) Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs. Ballieres Clin Rheumatol 3:247–269Google Scholar
  23. 23.
    Wiener H, Turnheim K, Van Os CH (1989) Rabbit distal colon epithelium: I. Isolation and characterization of basolateral plasma membrane vesicles from surface and crypt cells. J Membr Biol 110:147–162Google Scholar
  24. 24.
    Brown MD, Dudeja PK, Brasitus TA (1988) S-adenosyl-L-methionine modulates Na++K+-ATPase activity in rat colonic basolateral membranes. Biochem J 251:215–222Google Scholar
  25. 25.
    Dudeja PK, Foster ES, Dahiya R, Brasitus TA (1987) Modulation of Na+−H+ exchange by ethinyl estradiol in rat colonic brush-border membrane vesicles. Biochim Biophys Acta 899:222–228Google Scholar
  26. 26.
    Powell DW, Berschneider HM, Lawson LD, Martens H (1985) Regulation of water and ion movement in intestine. Ciba Found Symp 112:14–33Google Scholar
  27. 27.
    Brasitus TA (1983) Lipid dynamics and protein-lipid interactions in rat colonic epithelial cell basolateral membranes. Biochim Biophys Acta 728:20–30Google Scholar
  28. 28.
    Bershtein LM, Kovaleva IG (1985) Age-related changes in adenylate cyclase activity, lipid composition and lipid peroxidation in rat intestinal mucosa: comparison with the frequency of spontaneous tumors. Vopr Onkol 31:85–89Google Scholar
  29. 29.
    Brasitus TA, Davidson NO, Schlachter D (1985) Variations in dietary triacylglycerol saturation alter the lipid composition and fluidity of rat intestinal plasma membranes. Biochim Biophys Acta 863:309–319Google Scholar
  30. 30.
    McKibbin J, Arcolano L, Karlsson KA, Larson G, Thurin J, Brattain M (1988) Glycosphingolipids of cultured human colon carcinoma cells and their drug-resistant sublines. Biochim Biophys Acta 958:235–246Google Scholar
  31. 31.
    Merchant TE, Meneses P, Gierke LW, Den Otter W, Glonek T (1991) 31P magnetic resonance phospholipid profiles of neoplastic human breast tissues. Brit J Cancer 63:693–698Google Scholar
  32. 32.
    Mendelsohn J (1987) Principles of neoplasia. In: Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS (eds) Harrison's principles of internal medicine, 11th edn. McGraw-Hill, New York, pp 421–431Google Scholar
  33. 33.
    Dudeja PK, Foster ES, Brasitus TA (1986) Synthesis of phosphatidylcholine by two distinct methyltransferases in rat colonic brush-border membranes: evidence for extrinsic and intrinsic membrane activities. Biochim Biophys Acta 875:493–500Google Scholar
  34. 34.
    Rothman JE, Lenard J (1977) Membrane asymmetry. Science 195:743–753Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • T. E. Merchant
    • 1
    • 3
  • J. N. Kasimos
    • 4
  • P. W. de Graaf
    • 2
  • B. D. Minsky
    • 5
  • L. W. Gierke
    • 4
  • T. Glonek
    • 3
  1. 1.Department of PathologyUniversity Hospital UtrechtUtrechtThe Netherlands
  2. 2.Department of SurgeryUniversity Hospital UtrechtUtrechtThe Netherlands
  3. 3.MR LaboratoryChicago College of Osteopathic MedicineChicagoUSA
  4. 4.Department of PathologyChicago College of Osteopathic MedicineChicagoUSA
  5. 5.Department of Radiation OncologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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