Abstract
The low density lipoprotein receptor (LDLR) is a cell surface protein that binds with LDL, providing the cell with cholesterol for new membrane synthesis. Rapidly growing cells have high numbers of LDLRs, and these proteins have also been detected in neoplastic samples of human colorectal mucosa. Polyamines, putrescine, spermidine, and spermine, play an important role in cellular growth, and studies on colorectal cancers have demonstrated higher polyamine levels in neoplastic mucosa samples than in surrounding mucosa. The aim of this study was to investigate LDLR and polyamine levels in the neoplastic tissue of 43 patients (28 males and 15 females) with colorectal adenocarcinoma, using enzymatic immunoassay and high performance liquid chromatography, respectively. Specimens of neoplastic mucosa were considered LDLR-positive or LDLR-negative when the amount of bound anti-LDLR Ab/mg protein), respectively. Twenty-one subjects were LDLR-positive and 22 LDLR-negative. Polyamine levels (nmol/g tissue) were higher in LDLR-positive specimens; this increase was significant for total polyamines (P<0.05). These findings, reporting the presence of increased polyamine content in LDLR-positive colorectal neoplastic specimens, suggest an association between LDLR levels and gastrointestinal neoplastic proliferative activity.
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Beisiegel U, Schneider WJ, Brown MS, Goldstein JL. Immunoblot analysis of low density lipoprotein receptors in fibroblasts from subjects with familial hypercholesterolemia. J Biol Chem 1982;257:13150–13156.
Fong LG, Bonney E, Kosek JC, Cooper AD, Immunohistochemical localization of low density lipoprotein receptors in adrenal gland, liver, and intestine. J Clin Invest 1989;84:847–856.
Rudling MJ, Peterson CO: A simple binding assay for the determination of low-density lipoprotein receptors in cell homogenates. Biochem Biophys Acta 1985;833:359–365.
Srere PA, Chaikoff IL, Treitman SS, Burstein LS. The extrahepatic synthesis of cholesterol. J Biol Chem 1950;182:629–634.
Witte LD, Cornicelli JA, Miller RW, Goodmann DS: Effects of platelet-derived and endothelial cell-derived growth factors on the low density lipoprotein receptor pathway in cultured human fibroblasts. J Biol Chem 1982;257:5392–5401.
Rose G, Blackburn H, Keys A, et al. Colon cancer and blood cholesterol. Lancet 1974;I:181–183.
Caruso MG, Notarnicola M, Cavallini A, et al. Demonstration of low density lipoprotein receptor in human colonic carcinoma and surrounding mucosa by immunoenzymatic assay. Ital J Gastroenterol 1993;25:361–367.
Tabor CV, Tabor H. Polyamines. Annu Rev Biochem 1984;53:749–790.
Sakai TT, Cohen SS. Effects of polyamines on the structure and reactivity of tRNA. Prog Nucleic Acid Res Mol Biol 1976;17:15–26.
Di Leo A, Linsalata M, Cavallini A, et al. Sex steroid hormone receptor, epidermal growth factor receptor, and polyamines in human colorectal cancer. Dis Colon Rectum 1992;35:305–309.
Russo F, Linsalata M, Messa C, et al. Polyamines and estrogen-receptor concentrations in human colorectal carcinomas. Ital J Gastroenterol 1992;24:8–12.
Linsalata M, Russo F, Cavallini A, et al. Polyamines, diamine oxidase, and ornithine decarboxylase activity in colorectal cancer and in normal surrounding mucosa. Dis Colon Rectum 1993;36:662–667.
Grimaux M, Mady E, Remvikos Y, et al. A simplified immunoenzymetric assay of the epidermal growth factor in breast tumours: Evaluation in 282 cases. Int J Cancer 1990;45:255–262.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193:265–275.
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986;232:34–47.
Seiler N. Polyamine metabolism. Digestion 1990;46(Suppl 2):319–330.
May K, Kraemer FR, Chen J, Cooper AD. Elisa measurement of LDL-receptors. J Lip Res 1990;31:1683–1691.
Viallard V, Lacombe C, Trocheris V, et al. Metabolism of low density lipoprotein in differentiated and undifferentiated HT29 colon cancer cells. Int J Cancer 1990;46:320–325.
Fabricant M, Broitman SA. Evidence for deficiency of low density lipoprotein receptor on human colonic carcinoma cell lines. Cancer Res 1990;50:632–636.
Gal D, MacDonald PC, Porter JC, et al. Effect of the cell density and confluency on cholesterol metabolism in cancer cells in monolayer culture. Cancer Res 1981;473–477.
Windler EET, Kovaner PT, Chao YS, et al. The estradiolstimulated lipoprotein receptor of rat liver. A binding site that mediates the uptake of rat lipoproteins B and E. J Biol Chem 1980;255:10464–10471.
Rudling MJ, Stahle L, Peterson CO, Skoog L. Content of low density lipoprotein receptor in breast cancer tissue related to survival of patients. BMJ 1986;292:580–582.
Murakami M, Ushio Y, Mihara Y, et al. Cholesterol uptake by human glioma cells via receptor-mediated endocytosis of low density lipoprotein. J Neurosurg 1990;73:760–767.
Ho YK, Smith RG, Brown MS, Goldstein J. Low density lipoprotein (LDL) receptor activity in human acute myelogenous leukemia cells. Blood 1978;52:1099–1114.
Vitols S, Peterson C, Larsson O, et al. Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo. Cancer Res 1992;52:6244–6247.
Russel DW, Schneider WJ, Yamamoto T, et al. Domain map of the LDL receptor: Sequence homology with the epidermal growth factor precursor. Cell 1984;37:577–586.
Henriksson P, Eriksson M, Ericsson S, et al. Hypocholesterolemia and increased elimination of low density lipoproteins in metastatic cancer of the prostate. Lancet 1989;II:1178–1180.
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Notarnicola, M., Linsalata, M., Caruso, M.G. et al. Low density lipoprotein receptors and polyamine levels in human colorectal adenocarcinoma. J Gastroenterol 30, 705–709 (1995). https://doi.org/10.1007/BF02349635
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DOI: https://doi.org/10.1007/BF02349635