Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 2000 Jul 1;349(Pt 1):189–193. doi: 10.1042/0264-6021:3490189

Lithocholic acid and sulphated lithocholic acid differ in the ability to promote matrix metalloproteinase secretion in the human colon cancer cell line CaCo-2.

B Halvorsen 1, A C Staff 1, S Ligaarden 1, K Prydz 1, S O Kolset 1
PMCID: PMC1221136  PMID: 10861227

Abstract

The human colon carcinoma cell line CaCo-2 has the ability to sulphate the secondary bile acid lithocholic acid (LA), whereas other primary or secondary bile acids were not sulphated [Halvorsen, Kase, Prydz, Gharagozlian, Andresen and Kolset (1999) Biochem. J. 343, 533--539]. To study the biological implications of this modification, CaCo-2 cells were incubated with either LA or sulphated lithocholic acid (3-sulpholithocholic acid, SLA), and in some experiments with taurine-conjugated lithocholic acid. Increased secretion of matrix metalloproteinases (MMPs) correlates with transformation of colon epithelial cells. When CaCo-2 cells were incubated with LA, the secretion of MMP-2 was found to increase approx. 60% when analysed by gelatin zymography, and 80% when analysed by Western blotting. SLA, in contrast, did not affect the level of MMP-2 secretion, and after zymography the level of enzyme activity was 78% of control values after 18 h incubation. The secretion of MMPs is linked to increased cellular invasion and, in tumours, to increased capacity for metastasis. The ability of CaCo-2 cells to invade in a chamber assay was stimulated after exposure to LA, whereas SLA-treated cells did not differ from control cells. LA therefore seems to induce a more invasive CaCo-2 cell phenotype, as judged by the two parameters tested, whereas the sulphated counterpart, SLA, did not have these effects. Sulphation of LA in the colon may be an important mechanism to decrease the potential LA has to promote a malignant epithelial phenotype.

Full Text

The Full Text of this article is available as a PDF (145.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brown P. D. Matrix metalloproteinases in gastrointestinal cancer. Gut. 1998 Aug;43(2):161–163. doi: 10.1136/gut.43.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Halvorsen B., Kase B. F., Prydz K., Garagozlian S., Andresen M. S., Kolset S. O. Sulphation of lithocholic acid in the colon-carcinoma cell line CaCo-2. Biochem J. 1999 Nov 1;343(Pt 3):533–539. [PMC free article] [PubMed] [Google Scholar]
  3. Hirano F., Tanada H., Makino Y., Okamoto K., Hiramoto M., Handa H., Makino I. Induction of the transcription factor AP-1 in cultured human colon adenocarcinoma cells following exposure to bile acids. Carcinogenesis. 1996 Mar;17(3):427–433. doi: 10.1093/carcin/17.3.427. [DOI] [PubMed] [Google Scholar]
  4. Hooper L. V., Manzella S. M., Baenziger J. U. From legumes to leukocytes: biological roles for sulfated carbohydrates. FASEB J. 1996 Aug;10(10):1137–1146. doi: 10.1096/fasebj.10.10.8751716. [DOI] [PubMed] [Google Scholar]
  5. Itoh Y., Ito A., Iwata K., Tanzawa K., Mori Y., Nagase H. Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface. J Biol Chem. 1998 Sep 18;273(38):24360–24367. doi: 10.1074/jbc.273.38.24360. [DOI] [PubMed] [Google Scholar]
  6. Kanda T., Foucand L., Nakamura Y., Niot I., Besnard P., Fujita M., Sakai Y., Hatakeyama K., Ono T., Fujii H. Regulation of expression of human intestinal bile acid-binding protein in Caco-2 cells. Biochem J. 1998 Feb 15;330(Pt 1):261–265. doi: 10.1042/bj3300261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kishida T., Taguchi F., Feng L., Tatsuguchi A., Sato J., Fujimori S., Tachikawa H., Tamagawa Y., Yoshida Y., Kobayashi M. Analysis of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects. J Gastroenterol. 1997 Jun;32(3):306–311. doi: 10.1007/BF02934485. [DOI] [PubMed] [Google Scholar]
  8. Kjellén L., Lindahl U. Proteoglycans: structures and interactions. Annu Rev Biochem. 1991;60:443–475. doi: 10.1146/annurev.bi.60.070191.002303. [DOI] [PubMed] [Google Scholar]
  9. Latta R. K., Fiander H., Ross N. W., Simpson C., Schneider H. Toxicity of bile acids to colon cancer cell lines. Cancer Lett. 1993 Jul 16;70(3):167–173. doi: 10.1016/0304-3835(93)90227-z. [DOI] [PubMed] [Google Scholar]
  10. Makishima M., Okamoto A. Y., Repa J. J., Tu H., Learned R. M., Luk A., Hull M. V., Lustig K. D., Mangelsdorf D. J., Shan B. Identification of a nuclear receptor for bile acids. Science. 1999 May 21;284(5418):1362–1365. doi: 10.1126/science.284.5418.1362. [DOI] [PubMed] [Google Scholar]
  11. Mandon E. C., Milla M. E., Kempner E., Hirschberg C. B. Purification of the Golgi adenosine 3'-phosphate 5'-phosphosulfate transporter, a homodimer within the membrane. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10707–10711. doi: 10.1073/pnas.91.22.10707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nieuw Amerongen A. V., Bolscher J. G., Bloemena E., Veerman E. C. Sulfomucins in the human body. Biol Chem. 1998 Jan;379(1):1–18. doi: 10.1515/bchm.1998.379.1.1. [DOI] [PubMed] [Google Scholar]
  13. Parks D. J., Blanchard S. G., Bledsoe R. K., Chandra G., Consler T. G., Kliewer S. A., Stimmel J. B., Willson T. M., Zavacki A. M., Moore D. D. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999 May 21;284(5418):1365–1368. doi: 10.1126/science.284.5418.1365. [DOI] [PubMed] [Google Scholar]
  14. Podesta M. R., Murphy G. M., Dowling R. H. Measurement of faecal bile acid sulphates. J Chromatogr. 1980 Jun 13;182(3-4):293–300. doi: 10.1016/s0378-4347(00)81477-2. [DOI] [PubMed] [Google Scholar]
  15. Pongracz J., Clark P., Neoptolemos J. P., Lord J. M. Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids. Int J Cancer. 1995 Mar 29;61(1):35–39. doi: 10.1002/ijc.2910610107. [DOI] [PubMed] [Google Scholar]
  16. Salmivirta M., Safaiyan F., Prydz K., Andresen M. S., Aryan M., Kolset S. O. Differentiation-associated modulation of heparan sulfate structure and function in CaCo-2 colon carcinoma cells. Glycobiology. 1998 Oct;8(10):1029–1036. doi: 10.1093/glycob/8.10.1029. [DOI] [PubMed] [Google Scholar]
  17. Takahashi A., Tanida N., Kawaura A., Nishikawa M., Shimoyama T. Sulphated bile acid per se inhibits colonic carcinogenesis in mice. Eur J Cancer Prev. 1993 Mar;2(2):161–167. doi: 10.1097/00008469-199303000-00009. [DOI] [PubMed] [Google Scholar]
  18. Takikawa H., Tomita J., Takemura T., Yamanaka M. Cytotoxic effect and uptake mechanism by isolated rat hepatocytes of lithocholate and its glucuronide and sulfate. Biochim Biophys Acta. 1991 Jan 31;1091(2):173–178. doi: 10.1016/0167-4889(91)90058-6. [DOI] [PubMed] [Google Scholar]
  19. Vassalli J. D., Pepper M. S. Tumour biology. Membrane proteases in focus. Nature. 1994 Jul 7;370(6484):14–15. doi: 10.1038/370014a0. [DOI] [PubMed] [Google Scholar]
  20. Walker S., Stiehl A., Raedsch R., Klöters P., Kommerell B. Colonic absorption of sulfated and nonsulfated bile acids in rat. Digestion. 1986;33(1):1–6. doi: 10.1159/000199268. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES