Abstract
The fatty acid compositions of several tumors have been modified sufficiently to alter some of their properties and functions. These modifications were produced in culture by adding specific fatty acids to the growth medium or by feeding fat-supplemented diets to tumor-bearing mice. The phospholipid fatty acid composition of the plasma membrane was modified, but there were no changes in membrane phospholipid or cholesterol content or in phospholipid head group composition. Each of the most abundant membrane phosphoglyceride fractions exhibited some degree of fatty acid modification. Electron spin resonance measurements with nitroxystearate spin probes indicated that the fatty acid modifications were sufficient to alter the physical properties of the plasma membrane. The K ′ m for methotrexate uptake was reduced when the L1210 leukemia cells were enriched in linoleic acid. Even when the kinetics of uptake at 37 C were not altered, such as for melphalan and phenylalanine uptake, the temperature transition of transport was modified, indicating that these transport systems also are responsive to the membrane fatty acid modifications. Enrichment with highly polyunsaturated fatty acid did not affect either the growth rate or radiosensitivity of the L1210 leukemia. However, the sensitivity of the L1210 cells to the cytotoxic effects of Adriamycin and hyperthermia was increased. These findings suggest the possibility that fatty acid modification of tumors may be a useful adjunct to certain currently available therapeutic modalities.
Similar content being viewed by others
References
Spector, A.A., and Yorek, M.A. (1985)J. Lipid Res. 26, 1015–1035.
Spector, A.A., Mathur, S.N., Kaduce, T.L., and Hyman, B.T. (1981)Prog. Lipid Res. 19, 155–186.
Spector, A.A. (1975)Prog. Biochem. Pharm. 10, 42–75.
Burns, C.P., Luttenegger, D.G., Dudley, D.T., Buettner, G.R., and Spector, A.A. (1979)Cancer Res. 39, 1726–1732.
Kaduce, T.L., Awad, A.B., Fontenelle, L.J., and Spector, A.A. (1977)J. Biol. Chem. 252, 6624–6630.
Guffy, M.M., North, J.A., and Burns, C.P. (1984)Cancer Res. 44, 1863–1866.
King, M.E., and Spector, A.A. (1978)J. Biol. Chem. 253, 6493–6501.
Yorek, M.A., Strom, D.K., and Spector, A.A. (1984)J. Neurochem. 42, 254–261.
Simon, I., Mathur, S.N., Lokesh, B.R., and Spector, A.A. (1984)Biochim. Biophys. Acta 804, 245–252.
Yoo, T.-J., Chiu, H.C., Spector, A.A., Whiteaker, R.S., Denning, G.M., and Lee, N.F. (1980)Cancer Res. 40, 1084–1090.
Burns, C.P., Luttenegger, D.G., and Spector, A.A. (1978)J. Natl. Cancer Inst. 61, 513–515.
Guffy, M.M., Rosenberger, J.A., Simon, I., and Burns, C.P. (1982)Cancer Res. 42, 3625–3630.
Liepkalns, V.A., and Spector, A.A. (1975)Biochem. Biophys. Res. Commun. 63, 1043–1047.
Burns, C.P., Luttenegger, D.G., Wei, S.-P.L., and Spector, A.A. (1977)Lipids 12, 747–752.
Awad, A.B., and Spector, A.A. (1976)Biochim. Biophys. Acta 426, 723–731.
Awad, A.B., and Spector, A.A. (1976)Biochim. Biophys. Acta 450, 239–251.
Brenneman, D.E., Kaduce, T.L., and Spector, A.A. (1977)J. Lipid Res. 18, 582–591.
Abraham, S., and Hillyard, L.A. (1983)J. Natl. Cancer Inst. 71, 601–605.
Cave, W.T., and Jurkowski, J.J. (1984)J. Natl. Cancer Inst. 73, 185–191.
Jurkowski, J.J., and Cave, W.T. (1985)J. Natl. Cancer Inst. 74, 1145–1150.
Karmali, R.A., Marsh, J., and Fuchs, C. (1984)J. Natl. Cancer Inst. 73, 457–461.
King, M.E., Stavens, B.W., and Spector, A.A. (1977)Biochemistry 16, 5280–5285.
Simon, I., Burns, C.P., and Spector, A.A. (1982)Cancer Res. 42, 2715–2721.
Hyman, B.T., and Spector, A.A. (1982)J. Neurochem. 38, 650–656.
Yorek, M.A., Hyman, B.T., and Spector, A.A. (1983)J. Neurochem. 40, 70–78.
Burns, C.P., and Dudley, D.T. (1982)Biochem. Pharmacol. 31, 2116–2119.
Im, W.B., Duetchler, J.T., and Spector, A.A. (1979)Lipids 14, 1003–1009.
Ip, M.M., and Ip, C. (1981)Nutr. Cancer 3, 27–34.
Ramu, A., Glaubiger, D., and Weintraub, H. (1984)Cancer Treat. Rep. 68, 637–641.
Ramu, A., Glaubiger, D., Magrath, I.T., and Joshi, A. (1983)Cancer Res. 43, 5533–5537.
Siegfried, J.A., Kennedy, K.A., Sartorelli, A.C., and Tritton, T.R. (1983)J. Biol. Chem. 258, 339–343.
Burns, C.P., and North, J.A. (1986)Biochim. Biophys. Acta 888, 10–17.
Guffy, M.M., Oberley, L.W., and Burns, C.P. (1981)Proc. Amer. Assoc. Cancer Res. 22, 64 (abstr.).
Bhuyan, B.K. (1979)Cancer Res. 39, 2277–2284.
Giovanella, B.C., Stehlin, J.S., Shepard, R.C., and Williams, L.J. (1979)Cancer Res. 39, 2236–2241.
Burns, C.P., Rosenberger, J.A., and Luttenegger, D.G. (1983)Ann. Nutr. Metab. 27, 268–277.
Carroll, K.K., and Khor, H.T. (1971)Lipids 6, 415–420.
Carroll, K.K., and Hopkins, G.J. (1979)Lipids 14, 155–158.
Welsch, C.W., and Aylsworth, C.F. (1983)J. Natl. Cancer Inst. 70, 215–221.
Ip, C., Carter, C.A., and Ip, M.M. (1985)Cancer Res. 45, 1997–2001.
Rogers, A.E., Conner, B., Boulanger, C., and Lee, S. (1986)Lipids 21, 257–280.
Roebuck, B.D. (1986)Lipids 21, 281–284.
Braden, L.M., and Carroll, K.K. (1986)Lipids 21, 258–288.
Ip, C., Yip, P., and Bernardis, L.L. (1980)Cancer Res. 40, 374–378.
Ip, C. (1980)Cancer Res. 40, 2785–2789.
Aylsworth, C.F., Jone, C., Trosko, J.E., Meites, J., and Welsch, C.W. (1984)Cancer Res. 72, 637–645.
Author information
Authors and Affiliations
About this article
Cite this article
Burns, C.P., Spector, A.A. Membrane fatty acid modification in tumor cells: A potential therapeutic adjunct. Lipids 22, 178–184 (1987). https://doi.org/10.1007/BF02537299
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02537299