Lipoproteins, Cell Proliferation and Cancer
In experimental animals, diets high in polyunsaturated fatty acids (USF) greatly promote tumorigenesis relative to the same animals fed saturated fat (SF)1–6. It appears that the tumor-promoting properties of a high fat diet are more a function of fatty acid composition than of fat content per se or total caloric intake5. Various mechanisms that were examined to explain the promotion of tumorigenesis by USF diet include: alterations in hormone levels, membrane fluidity, intracellular communication, prostaglandins, protein kinases, immune system and cell proliferation5. In spite of studies by cancer biologists and nutritionists, the exact mechanism(s) by which USF diets promote tumorigenesis is not well understood. It is likely that the tumor promoting properties of high USF diets may be related to their capacity to eliminate bile acids, stimulate de novo cholesterogenesis and decrease serum cholesterol ester levels7. Moreover, in various experimental tumor model systems3–5 and in epidemiological studies8, the serum cholesterol and triglyceride levels were found to be reduced. However, a cause and effect relationship between low serum low density lipoproteins (LDL) and promotion of cancer has not been explored thoroughly. Nonetheless, it is widely accepted that there is a cause and effect relationship between serum LDL and coronary heart disease (CHD) and that a reduction in serum LDL will greatly reduce the risk of CHD9.
KeywordsSerum Lipoprotein Acinar Cell Carcinoma Skin Allograft Choline Deficient Research Clinic Coronary Primary Prev
E. A. Alcantara and E. W. Speckman, Diet, Nutrition and Cancer, Am. J. Clin. Nutr.
29:1035 (1976).PubMedGoogle Scholar
B. D. Roebuck, J. D. Yager, D. S. Longnecker and S. A. Willpone, Promotion of unsaturated fat of azaserine induced pancreatic carcinogenesis in the rat, Cancer Res.
41:3961 (1981).PubMedGoogle Scholar
L. A. Cohen, D. A. Thompson, K. Choi, R. A. Karmali and D. P. Rose, Dietary fat and mammary cancer II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fats: Association with tumor incidence patterns, J. Natl. Cancer Inst.
77:43 (1986).PubMedGoogle Scholar
S. A. Broitman, J. J. Vitale, E. Vavrousek-Jakuba and L. S. Gottlieb, Polyunsaturated fat, cholesterol and large bowel tumorigenesis, Cancer
40:2455 (1977).PubMedCrossRefGoogle Scholar
C. W. Welsch, Host factors affecting the growth of carcinogen induced rat mammary carcinomas: A review and tribute to Charles Brenton Higgins, Cancer Res.
45:3415 (1985).PubMedGoogle Scholar
K. N. Rao, H. Shinozuka, H. W. Kunz and T. J. Gill III, Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (grc), Int. J. Cancer
34:113 (1984).PubMedCrossRefGoogle Scholar
C. S. Ramesha, R. Paul and J. Ganguly, Effect of dietary unsaturated oils on the biosynthesis of cholesterol and on biliary and fecal excretion of cholesterol and bile acids in rats, J. Nutr.
110:2149 (1980).PubMedGoogle Scholar
S. Graham, Dietary factors in the prevention of cancer, Transplantation Proceedings
16:392 (1984).PubMedGoogle Scholar
B. M. Rifkind, The lipid research clinics coronary primary prevention trial, Drugs
Suppl. 1, 53 (1986).CrossRefGoogle Scholar
J. J. Vitale and S. A. Broitman, Lipids and immune function, Cancer Res.
41:3706 (1981).PubMedGoogle Scholar
G. M. Kollmorgen, W. A. Sansing, A. A. Lehman, G. Fischer, R. E. Longley, S. S. Alexander, M. M. King and P. B. McCay, Inhibition of lymphocyte function in rats fed high fat diets, Cancer Res.
39:3458 (1979).PubMedGoogle Scholar
W. L. Kos, R. M. Loria, M. J. Snodgrass, D. Cohen, T. G. Thorpe and A. M. Kaplan, Inhibition of host resistance by nutritional hypercholesterolemia, Infect. Immun.
26:658 (1979).PubMedGoogle Scholar
M. I. McHugh, R. Wilkinson, R. W. Elliott, E. J. Field, P. Dewar, R. R. Hall, R. M. R. Taylor and P. R. Uldall, Immunosuppression with polyunsaturated fatty acids in renal transplantation, Transplantation
24:263 (1977).PubMedCrossRefGoogle Scholar
C. J. Meade and J. Mertin, Fatty acids and immunity, Adv. Lipid Res.
16:127 (1978).PubMedGoogle Scholar
C. J. Meade and J. Mertin, The mechanism of immunoinhibition by arachidonic acid and linoleic acid: effects on the lymphoid and reticuloendothelial systems, Inf. Archs. Allergy Appl. Immunol.
51:2 (1976).CrossRefGoogle Scholar
J. Mertin, Effects of polyunsaturated fatty acids on skin allograft survival and primary and secondary cytotoxic response in mice, Transplantation
21:1 (1976).PubMedCrossRefGoogle Scholar
J. Mertin and R. Hunt, Influence of polyunsaturated fatty acids on survival of skin allografts and tumor incidence in mice, Proc. Natl. Acad. Sci. USA
73:928 (1976).PubMedCrossRefGoogle Scholar
J. Ring, J. Seifert, J. Mertin and W. Brendel, Prolongation of skin allografts in rats by treatment with linoleic acid, Lancet
2:1331 (1974).PubMedCrossRefGoogle Scholar
P. R. Uldall, R. Wilkinson, M. I. McHugh, E. J. Field, B. K. Shenton, K. Baxby and R. M. R. Taylor, Linoleic acid and transplantation, Lancet
2:128 (1975).PubMedCrossRefGoogle Scholar
J. Mertin, Polyunsaturated fatty acids and cancer, Br. Med. J.
4:357 (1973).PubMedCrossRefGoogle Scholar
P. R. Uldall, R. Wilkinson, M. I. McHugh, E. J. Field, B. K. Shenton, K. Baxby, R. M. R. Taylor and J. Swinney, Unsaturated fatty acids and renal transplantation, Lancet
2:514 (1974).PubMedCrossRefGoogle Scholar
J. H. D. Miller, K. J. Zilkha, M. J. S. Langman, H. Playwright, A. D. Smith, J. Belin and R. H. S. Thompson, Double blind trial of linoleate supplementation of the diet in multiple sclerosis, Br. Med. J.
1:765 (1973).CrossRefGoogle Scholar
G. B. Otto, W. Dias da Silva, W. Gotze and I. Mota, Fundamentals of immunology, Springer-Verlag, New York, (1986).Google Scholar
J. V. Friend, S. O. Lock, M. I. Gurr and W. E. Parish, Effect of different dietary lipids on immune responses of Hartley strain guinea pigs, Int. Archs. Allergy Appl. Immunol.
62:292 (1980).CrossRefGoogle Scholar
J. H. Morse, L. D. Witte and D. S. Goodman, Inhibition of lymphocyte proliferation stimulated by lectins and allogenic cells by normal plasma lipoproteins, J. Exp. Med.
146:1791 (1977).PubMedCrossRefGoogle Scholar
C. C. Waddel, O. D. Taunton and J. J. Twomey, Inhibition of lymphoproliferation by hyperlipoproteinemic-plasma, J. Clin. Invest.
58:950 (1976).CrossRefGoogle Scholar
L. K. Curtiss, D. H. Deheer and T. S. Edgington, Influence of the immunoregulatory serum lipoprotein LDL-In on the in vivo
proliferation and differentiation of antigen-binding and antibody-secreting lymphocytes during a primary immune response, Cellular Immunol.
49:1 (1980).CrossRefGoogle Scholar
D. Y. Hui and J. A. K. Harmony, Inhibition of low density lipoproteins of mitogen-stimulated cyclic nucleotide production by lymphocytes, J. Biol. Chem.
255:1413 (1980).PubMedGoogle Scholar
D. Y. Hui and J. A. K. Harmony, Inhibition of Ca2+
accumulation in mitogen-activated lymphocytes: Role of membrane-bound plasma lipoproteins, Proc. Natl. Acad. Sci. USA
77:4764 (1980).PubMedCrossRefGoogle Scholar
F. Ito, Y. Takii, J. Suzuki and Y. Masamune, Reversible inhibition by human serum lipoproteins of cell proliferation, J. Cellular Physiol.
113:1 (1982).CrossRefGoogle Scholar
M. Macy, Y. Okano, A. D. Cardin, E. M. Avila and J. A. K. Harmony, Suppression of lymphocyte activation by plasma lipoproteins, Cancer Res.
(suppl.) 43:2496 (1983).Google Scholar
J. A. Cuthbert and P. E. Lipsky, Immunoregulation by low density lipoproteins in man: low density lipoprotein inhibits mitogen stimulated human lymphocyte proliferation after initial activation, J. Lipid Res.
24:1512 (1983).PubMedGoogle Scholar
K. N. Rao, S. Kottapally and H. Shinozuka, Lipid composition and 3-hydroxy-3-methylglutaryl-CoA reductase activity of acinar cell carcinoma of rat pancreas, Biochim. Biophys. Acta
759:74 (1983).PubMedCrossRefGoogle Scholar
K. N. Rao, S. Kottapally and H. Shinozuka, Acinar cell carcinoma of rat pancreas: Mechanism of deregulation of cholesterol metabolism Toxicol
12:62 (1984).Google Scholar
M. F. Meinem, H. F. Gabriel, E. D. Eskander and K. N. Rao, Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats, Br J. Cancer
56:45 (1987).CrossRefGoogle Scholar
K. N. Rao, Regulatory aspects of cholesterol metabolism in cells with different degrees of replication, Toxicol. Pathol.
14:430 (1986).PubMedCrossRefGoogle Scholar
M. D. Siperstein, Role of cholesterogenesis and isoprenoid synthesis in DNA replication and cell growth, J. Lipid Res.
25:1462 (1984).PubMedGoogle Scholar
H. W. Chen, H. J. Heiniger and A. A. Kandutsch, Relationship between sterol synthesis and DNA synthesis in phytohemagglutinin-stimulated mouse lymphocytes, Proc. Natl. Acad. Sci. USA
72:1950 (1975).PubMedCrossRefGoogle Scholar
K. N. Rao, S. Kottapally, E. D. Eskander, H. Shinozuka, S. Dessi and P. Pani, Acinar cell carcinoma of rat pancreas: Regulation of cholesterol esterification, Br. J. Cancer
54:305 (1986).PubMedCrossRefGoogle Scholar
P. S. Coleman and B. B. Lavietes, Membrane cholesterol and tumorigenesis, CRC Critical Rev. Biochem.
11:341 (1981).Google Scholar
A. Swann, M. H. Wiley and M. D. Siperstein, Tissue distribution of cholesterol feedback control in guinea pig, J. Lipid Res.
16:360 (1975).PubMedGoogle Scholar
J. M. Anderson and J. M. Dietschy, Regulation of sterol synthesis in 15 tissues of rat: II Role of rat and human high and low density plasma lipoproteins and of rat chylomicron remnants, J. Biol. Chem.
252:3652 (1977).Google Scholar
M. S. Brown, P. T. Kovanen and J. L. Goldstein, Regulation of plasma cholesterol by lipoprotein receptors, Science
212:628 (1981).PubMedCrossRefGoogle Scholar
M. J. Rudling and C. O. Peterson, LDL receptors in bovine tissues assayed as the heparin-sensitive binding of 125
I-labeled LDL in homogenates: relation between liver LDL receptors and serum cholesterol in the fetus and post term, Biochim. Biophys. Acta
836:96 (1985).PubMedCrossRefGoogle Scholar
E. Farber and D. S. R. Sarma, Biology of disease. Hepatocarcinogenes: A2 dynamic cellular perspective, Lab. Invest.
56:4 (1987).PubMedGoogle Scholar
L. I. Giambarresi, S. L. Katyal and B. Lombardi, Promotion of liver carcinogenesis in the rat by a choline-devoid diet: Role of liver cell necrosis and regeneration, Br. J. Cancer
46:825 (1982).PubMedCrossRefGoogle Scholar
N. Chandar, J. Amenta, J. C. Kandala and B. Lombardi, Liver cell turnover in rats fed a choline devoid diet, Carcinogenesis
8:669 (1987).PubMedCrossRefGoogle Scholar
J. C. Bieri, G. S. Stoewsand, G. M. Briggs, R. W. Phillips, J. C. Woodward and J. J. Knapka, Report of the American Institute of Nutrition. Ad hoc
committee on standards for nutritional studies, J. Nutr.
107:1340 (1977).Google Scholar
N. B. Myant, The biology of cholesterol and related steroids, William Heineman Medical Books Inc., London, (1981).Google Scholar
T. I. Pynadath and A. Z. Haghighi, Inhibition of thromboxane A2
synthesis in rats treated with phenobarbital, Prostaglandins Leukotrienes Med.
28:61 (1987).CrossRefGoogle Scholar
W. E. M. Lands, Fish and human health, Academic Press Inc., New York, (1986).Google Scholar
H. O. Bang and J. Dyerberg, The bleeding tendency in Greenland Eskimos, Danish Med. Bull.
27:202 (1980).PubMedGoogle Scholar
© Springer Science+Business Media New York 1988