Skip to main content
SpringerLink
Log in

Choline metabolism in breast cancer;2H-,13C- and31P-NMR studies of cells and tumors

  • Paper
  • Published:
Magnetic Resonance Materials in Physics, Biology and Medicine Aims and scope Submit manuscript

Abstract

Choline metabolism in breast cancer cells and tumors has been investigated by multinuclear NMR in order to provide the biochemical basis for the presence of high phosphocholine in breast carcinoma relative to benign breast tumors and normal breast tissue. Choline was found to be transported into MCF7 human breast cancer cells and rapidly phosphorylated to phosphocholine which was then accumulated in the cells to high concentrations. The increased level of phosphocholine did not affect the rate of synthesis of phosphatidylcholine, indicating tight regulation of this pathway. The incorporation of [l,2-13C]choline (100 μM) into phosphocholine and phosphatidylcholine after 24 h was 69.5 and 36% of the total respective pools. Incorporation of2H9-choline to tumors implanted in nude mice was achieved by infusing the deuterated choline to the blood circulation. The metabolism of deuterated choline was then monitored by2H localized MRS. The blood level of choline before the infusion was 58.6 ± 10.3 μM (measured by1H-NMR of plasma samples) and increased ∼ 5-fold during the infusion (measured by2H-NMR). This increase in the blood level resulted in a gradual increase of a signal at 3.2 ppm due to deuterated choline metabolites. It appears that the increased availability of choline in the blood circulation leads to accumulation of phosphocholine in the tumors by the same mechanism as in the cells. © 1998 Elsevier Science B.V. All rights reserved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Negendank W. Studies of human tumors by MRS: a review. NMR Biomed 1992;5:303–24.

    PubMed  CAS  Google Scholar 

  2. Oberhaensli RD, Hilton-Jones D, Bore PJ, Hands LJ, Rampling RP, et al. Biochemical investigation of human tumors in vivo with phosphorus-31 magnetic resonance spectroscopy. Lancet 1986;2:8–11.

    Article  PubMed  CAS  Google Scholar 

  3. Steen RG. Response of solid tumors to chemotherapy monitored by in vivo31P nuclear magnetic resonance spectroscopy: A review. Cancer Res 1989;49:4075–85.

    PubMed  CAS  Google Scholar 

  4. Negendank W, Li CW, Padavic-Shaller K, Murphy-Boesch J, Brown TR. Phospholipid metabolites in1H-decoupled31P MRS in vivo in human cancer: implications for experimental models and clinical studies. Anticancer Res 1996;16:1539–44.

    PubMed  CAS  Google Scholar 

  5. Ng TC, Grundfest S, Srinivasan V, Baldwin NJ, Majors AW, et al. Therapeutic response of breast carcinoma monitored by31P-MRS in situ. Magn Reson Med 1989; 10:125–34.

    Article  PubMed  CAS  Google Scholar 

  6. Sijens PE, Wijredeman HK, Moerland MA, Bakker GJG, Ver-moulen JWA, et al. Human breast cancer in vivo:1H- and31P-MR spectroscopy at 1.5 T. Radiology 1988;161:53–5.

    Google Scholar 

  7. Glanholm J, Leach MO, Collins DJ, Mansi J, Sharp JC, et al. In vivo31P magnetic spectroscopy for monitoring treatment response in breast cancer. Lancet 1989;l:1326–7.

    Article  Google Scholar 

  8. Degani H, Horowitz A, Itzchak Y. Breast tumors: Evaluation with31P-MR spectroscopy. Radiology 1986;161:53–5.

    PubMed  CAS  Google Scholar 

  9. Gribbestad IS, Fjosne HE, Kvinnsland S. In vitro proton NMR spectroscopy of extracts from human breast tumours and non-involved breast tissue. Anticancer Res 1993;13:1973–80.

    PubMed  CAS  Google Scholar 

  10. Gribbestad IS, Petersen SB, Fjosne HE, Kvinnsland S, Krane J.1H-NMR spectroscopic characterization of perchloric acid extracts from breast carcinomas and non-involved breast tissue. NMR Biomed 1994;7:181–94.

    Article  PubMed  CAS  Google Scholar 

  11. Gribbestad IS, Nilsen G, Fjosne HE, Haugen OA. Combined1H-MR spectroscopy and imaging of normal human breast and breast tumors. J Magn Reson Imag 1994;4:107.

    Article  Google Scholar 

  12. Roebuck JR, Lenkinski RE, Schnall MD. Spatially localized proton magnetic resonance spectroscopy of human breast disease at 1.5 T. Proc Int Soc Magn Resonance Med 1996;2:1247.

    Google Scholar 

  13. Barry PA, Mackinnon WB, Malycha P, Gillett D, Mountford CE. Benign breast lesions distinguished from invasive cancer by1H magnetic resonance spectroscopy on fine needle biopsy. Proc Int Soc Magn Resonance Med 1996;2:266.

    Google Scholar 

  14. Mackinnon WB, Barry PA, Malycha PL, Gillett DJ, Russell P, et al. Fineneedle biopsy specimens of benign breast lesions distinguished from invasive cancer ex vivo with proton MR spectroscopy. Radiology 1997;204:661–6.

    PubMed  CAS  Google Scholar 

  15. Ting YT, Sherr D, Degani H. Variations in the energy and phospholipid metabolism in normal and cancer human mammary epithelial cells. Anticancer Res 1996;16:1381–8.

    PubMed  CAS  Google Scholar 

  16. Katz-Brull R, Degani H. Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method. Anticancer Res 1996;16:1375–80.

    PubMed  CAS  Google Scholar 

  17. Chao CK, Pomfret EA, Zeisel SH. Uptake of choline by rat mammary-gland epithelial cells. Biochem J 1988;254:33–8.

    PubMed  CAS  Google Scholar 

  18. Zeisel SH, Costa KAD, Franklin PD, Alexander EA, Lamont JT, et al. Choline, an essential nutrient for humans. FASEB 1991;5:2093–8.

    CAS  Google Scholar 

  19. Zeisel SH. Choline deficiency. J Nutr Biochem 1990;l:332–49.

    Article  Google Scholar 

  20. Zeisel SH. Choline. Modern Nutrition in Health and Disease, 8th Edition. Philadelphia: Lea and Febiger, 1994.

    Google Scholar 

  21. Street JC, Szwergold BS, Matei C, Kappler F, Mahmood U, et al. Study of the metabolism of choline and phosphatidylcholine in tumors in vivo using phosphonium choline. Magn Reson Med 1997;38:769–75.

    Article  PubMed  CAS  Google Scholar 

  22. Katz-Brull R, Bendel P, Margalit R, Degani H. Quantitative in vivo kinetics of choline metabolism in breast cancer-a localized deuterium MRS study. MAGMA 1997;5:459.

    Google Scholar 

  23. Furman E, Rushkin E, Margalit R, Bendel P, Degani H. Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging. J Steroid Biochem Mol Biol 1992;43:189–95.

    Article  PubMed  CAS  Google Scholar 

  24. Degani H, Ronen SM, Furman E. Breast cancer: Spectroscopy and imaging of cells and tumors. In: Gillies R, editor. Magnetic resonance in physiology and medicine. San Diego: Academic Press, 1994.

    Google Scholar 

  25. Tyagi RK, Azrad A, Degani H, Salomon Y. Simultaneous extraction of cellular lipids and water-soluble metabolites: evaluation by NMR spectroscopy. Magn Reson Med 1996;35:194–200.

    Article  PubMed  CAS  Google Scholar 

  26. Haran EF, Maretzek AF, Goldberg I, Horowitz A, Degani H. Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. Cancer Res 1994;54:5511–4.

    PubMed  CAS  Google Scholar 

  27. Freeman JJ, Choi RL, Jenden DJ. Plasma choline: its turn over and exchange with brain choline. J Neurochem 1975;24:729–34.

    PubMed  CAS  Google Scholar 

  28. Ordidge RJ, Connelly A, Lohman JAB. Image-selected in vivo spectroscopy (ISIS). A new technique for spatially selective NMR spectroscopy. J Magn Reson 1986;66:283–94.

    CAS  Google Scholar 

  29. Sherr D, Rivenson D, Rushkin E, Degani H. Differences in the composition and metabolism of the phospholipids in normal and cancerous mammary epithelial cells. Proc Soc Magn Resonance 1994; 1:452.

    Google Scholar 

  30. Ronen SM, Rushkin E, Degani H. Lipid metabolism in large T47D human breast cancer spheroids:31P- and13C-NMR studies of choline and ethanolamine uptake. Biochim Biophys Acta 1992;1138:203–12.

    PubMed  CAS  Google Scholar 

  31. Ronen SM, Degani H. The application of13C-NMR to the characterization of phospholipid metabolism in cells. Magn Reson Med 1992;25:384–9.

    Article  PubMed  CAS  Google Scholar 

  32. Lynch MJ, Masters J, Pryor JP, Lindon JC, Spraul M, et al. Ultra high field NMR spectroscopic studies on human seminal fluid, seminal vesicle and prostatic secretions. J Pharm Biomed Anal 1994; 12:5–19.

    Article  PubMed  CAS  Google Scholar 

  33. Zeisel SH. Choline phospholipids: signal transduction and carcinogenesis. FASEB 1993;7:551–7.

    CAS  Google Scholar 

  34. Levenson AS, Jordan VC. MCF-7: The first hormone-responsive breast cancer cell line. Cancer Res 1997;57:3071–8.

    PubMed  CAS  Google Scholar 

  35. Pelech SL, Vance DE. Regulation of phosphatidylcholine biosynthesis. Biochim Biophys Acta 1984;779:217–51.

    PubMed  CAS  Google Scholar 

  36. Ronen SM, Rushkin E, Degani H. Lipid metabolism in T47D human breast cancer cells:31P and13C-NMR studies of choline and ethanolamine uptake. Biochim Biophys Acta 1991;1095:5–16.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Regulation, Weizmann Institute of Science, 76100, Rehovot, Israel

    R. Katz-Brull, R. Margalit, P. Bendel & H. Degani

Authors
  1. R. Katz-Brull
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Margalit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Bendel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Degani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Degani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katz-Brull, R., Margalit, R., Bendel, P. et al. Choline metabolism in breast cancer;2H-,13C- and31P-NMR studies of cells and tumors. MAGMA 6, 44–52 (1998). https://doi.org/10.1007/BF02662511

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02662511

Keywords

Search

Navigation