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. 1995 Mar;77(2):85–89.

Luminal and humoral influences on human rectal epithelial cytokinetics.

M G Thomas 1
PMCID: PMC2502129  PMID: 7793821

Abstract

Multiple genetic and environmental steps may underpin the development of human colorectal neoplasia, and experimental evidence suggests that promoters of colorectal cancer also induce colorectal epithelial cell hyperplasia. In vitro crypt cell production rate (CCPR) was measured to determine the effect of calcium, epidermal growth factor (EGF), vitamin D3 metabolites and synthetic analogues on human rectal epithelial cell proliferation. In a double-blind trial of oral calcium supplementation, CCPR was reduced by 49% in patients with familial adenomatous polyposis (FAP), but there was no effect on established neoplasia. In control tissue, the active form of vitamin D3 (1,25(OH)2D3) reduced rectal CCPR by 57% at 1 microM, 55% at 10 nM and 45% at 100 pM. Likewise, in tissue taken from patients with FAP, 1,25(OH)2D3 reduced CCPR by 52%. Vitamin D3 has profound effects on calcium metabolism, but synthetic analogues can avoid these. The effects of a synthetic analogue (MC-903) on human rectal CCPR were therefore studied. MC-903 (10(-7) M) reduced CCPR in control tissue by 51%, and in FAP tissue by 52% at 10(-6) M and 51% at 10(-7) M. In addition, MC-903 and a related analogue, EB 1089, produced a clear-cut dose-dependent inhibition of both HT-29 and Caco2 colorectal cancer cells maintained in culture. Hence, vitamin D3 and its analogues can reduce the rate of cell proliferation in normal, premalignant and malignant colorectal epithelial cells and might therefore have future therapeutic uses as chemoprotective or chemotherapeutic agents. Lastly, EGF increases CCPR by 102% in FAP tissue that expresses the EGF receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Appleton G. V., Davies P. W., Bristol J. B., Williamson R. C. Inhibition of intestinal carcinogenesis by dietary supplementation with calcium. Br J Surg. 1987 Jun;74(6):523–525. doi: 10.1002/bjs.1800740635. [DOI] [PubMed] [Google Scholar]
  2. Appleton G. V., Owen R. W., Wheeler E. E., Challacombe D. N., Williamson R. C. Effect of dietary calcium on the colonic luminal environment. Gut. 1991 Nov;32(11):1374–1377. doi: 10.1136/gut.32.11.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barsoum G. H., Hendrickse C., Winslet M. C., Youngs D., Donovan I. A., Neoptolemos J. P., Keighley M. R. Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation. Br J Surg. 1992 Jun;79(6):581–583. doi: 10.1002/bjs.1800790639. [DOI] [PubMed] [Google Scholar]
  4. Brehier A., Thomasset M. Human colon cell line HT-29: characterisation of 1,25-dihydroxyvitamin D3 receptor and induction of differentiation by the hormone. J Steroid Biochem. 1988 Feb;29(2):265–270. doi: 10.1016/0022-4731(88)90275-0. [DOI] [PubMed] [Google Scholar]
  5. Caspari R., Friedl W., Mandl M., Möslein G., Kadmon M., Knapp M., Jacobasch K. H., Ecker K. W., Kreissler-Haag D., Timmermanns G. Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer. Lancet. 1994 Mar 12;343(8898):629–632. doi: 10.1016/s0140-6736(94)92634-4. [DOI] [PubMed] [Google Scholar]
  6. Garland C., Shekelle R. B., Barrett-Connor E., Criqui M. H., Rossof A. H., Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985 Feb 9;1(8424):307–309. doi: 10.1016/s0140-6736(85)91082-7. [DOI] [PubMed] [Google Scholar]
  7. Giuliano A. R., Franceschi R. T., Wood R. J. Characterization of the vitamin D receptor from the Caco-2 human colon carcinoma cell line: effect of cellular differentiation. Arch Biochem Biophys. 1991 Mar;285(2):261–269. doi: 10.1016/0003-9861(91)90358-p. [DOI] [PubMed] [Google Scholar]
  8. Gullick W. J., Hughes C. M., Mellon K., Neal D. E., Lemoine N. R. Immunohistochemical detection of the epidermal growth factor receptor in paraffin-embedded human tissues. J Pathol. 1991 Aug;164(4):285–289. doi: 10.1002/path.1711640403. [DOI] [PubMed] [Google Scholar]
  9. Lipkin M. Biomarkers of increased susceptibility to gastrointestinal cancer: new application to studies of cancer prevention in human subjects. Cancer Res. 1988 Jan 15;48(2):235–245. [PubMed] [Google Scholar]
  10. Lipkin M., Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985 Nov 28;313(22):1381–1384. doi: 10.1056/NEJM198511283132203. [DOI] [PubMed] [Google Scholar]
  11. Lointier P., Meggouh F., Dechelotte P., Pezet D., Ferrier C., Chipponi J., Saez S. 1,25-Dihydroxyvitamin D3 receptors and human colon adenocarcinoma. Br J Surg. 1991 Apr;78(4):435–439. doi: 10.1002/bjs.1800780416. [DOI] [PubMed] [Google Scholar]
  12. Lointier P., Wargovich M. J., Saez S., Levin B., Wildrick D. M., Boman B. M. The role of vitamin D3 in the proliferation of a human colon cancer cell line in vitro. Anticancer Res. 1987 Jul-Aug;7(4B):817–821. [PubMed] [Google Scholar]
  13. Rainey J. B., Davies P. W., Williamson R. C. Relative effects of ileal resection and bypass on intestinal adaptation and carcinogenesis. Br J Surg. 1984 Mar;71(3):197–202. doi: 10.1002/bjs.1800710309. [DOI] [PubMed] [Google Scholar]
  14. Steele G., Jr Accomplishment and promise in the understanding and treatment of colorectal cancer. Lancet. 1993 Oct 30;342(8879):1092–1096. doi: 10.1016/0140-6736(93)92068-5. [DOI] [PubMed] [Google Scholar]
  15. Studzinski G. P., Bhandal A. K., Brelvi Z. S. Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3. Cancer Res. 1985 Aug;45(8):3898–3905. [PubMed] [Google Scholar]
  16. Thomas M. G., Tebbutt S., Williamson R. C. Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. Gut. 1992 Dec;33(12):1660–1663. doi: 10.1136/gut.33.12.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Thomas M. G., Thomson J. P., Williamson R. C. Oral calcium inhibits rectal epithelial proliferation in familial adenomatous polyposis. Br J Surg. 1993 Apr;80(4):499–501. doi: 10.1002/bjs.1800800432. [DOI] [PubMed] [Google Scholar]

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