Skip to main content
SpringerLink
Log in

Differentiation of Human Colon Cancer Cells

  • Chapter
Pharmaceutical Applications of Cell and Tissue Culture to Drug Transport

Part of the book series: NATO ASI Series ((NSSA,volume 218))

Abstract

As it is the case for many tissues, there has been an increasing interest over the last decade in the use of cell cultures for studies related to the functions of the intestinal epithelium. These studies have been essentially performed with either organ cultures or primary cultures1,2. However there are some limitations in the application of such systems as they are difficult to manipulate, do not allow reproducible dynamic studies, and are not homogenous. An ideal tool would be the use of established differentiated cell lines originating from normal tissues. However, and despite attempts from a number of laboratories1,2,3, it has not been possible to establish such cell lines so far. In fact, the only cell lines that have been established have regularly failed to express any of the characteristics of terminal differentiation which would make them useful for studies related to the physiological functions of the intestinal epithelium1,2,3. This failure has been however circumvented by the finding that cell lines established from human colon carcinomas are able to express in culture most of the differentiation characteristics and functions normally associated with the human intestinal epithelium1,2,4,5,6. As appropriate as these cell lines may be for studying a number of functions related to the intestinal epithelium, it must be emphasized that, although these cells are closely similar to, and share a number of physiological properties with intestinal cells, they are not small intestinal, but colonic cells, and are not normal, but malignant cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. M. Kedinger, K. Haffen, and P. Simon-Asmmann, Intestinal tissue and cell cultures. Differentiation, 36: 71–85 (1985).

    Article  Google Scholar 

  2. M. Neutra, and D. Louvard, Differentiation of intestinal cells in vitro. In: Functional Epithelial Cells in Culture. Alan R. Liss, Inc., p. 363-398 (1989).

    Google Scholar 

  3. A. Quaroni, and R.J. May, Establishment and characterization of intestinal epithelial cell cultures. In: Methods in Cell Biology, edited by G.C. Harris, B.F. Trump, and G.D. Stoner, Academic Press, New York, vol. 21B, p. 403–427 (1980).

    Google Scholar 

  4. M. Rousset, The human colon carcinoma cell lines HT-29 and Caco-2: two in vitro models for the study of intestinal differentiation. Biochimie, 68: 1035–1040 (1986).

    Article  PubMed  CAS  Google Scholar 

  5. C.L. Laboisse, Differentiation of colon cells in culture. In: The Cell and Molecular Biology of Colon Cancer. L.H. Augenlicht ed., CRC Press, pp 28-45 (1989).

    Google Scholar 

  6. A. Zweibaum, M. Laburthe, E. Grasset, and D. Louvard, The use of cultured cell lines in studies of intestinal cell differentiation and function. In: Handbook of Physiology, vol. Intestinal Transport of the Gastrointestinal System (M. Field, and R.A. Frizzell, eds), Am. Physiol. Soc. (1989) (in press).

    Google Scholar 

  7. F.J. Primus, C.A. Clark, and D.G. Goldenberg, Immunoperoxidase localization of carcinoembryonic antigen in normal human intestinal mucosa. J. Natl. Cancer Inst., 63: 1031–1039 (1981).

    Google Scholar 

  8. A. Bretscher, and K. Weber, Villin: the major microfilamentassociated protein of the intestinal microvillus. Proc. Natl. Acad. Sci. USA, 76: 2321–2325 (1979).

    Article  PubMed  CAS  Google Scholar 

  9. G. Semenza, Anchoring and biosynthesis of stalked brush border membrane proteins: glycosidases and peptidases of enterocytes and of renal tubuli. Annu. Rev. Cell Biol., 2: 255–314 (1986).

    Article  PubMed  CAS  Google Scholar 

  10. A. Zweibaum, H.P. Hauri, E. Sterchi, I. Chantret, K. Haffen, J. Bamat, and B. Sordat, Immunohistological evidence obtained with monoclonal antibodies of small intestinal brush border hydrolases in human colon cancers and foetal colons. Int. J. Cancer, 34: 591–598 (1984).

    Article  PubMed  CAS  Google Scholar 

  11. A. Zweibaum, N. Triadou, M. Kedinger, C. Augeron, S. Robine-Léon, M. Pinto, M. Rousset, and K. Haffen, Sucrase-isomaltase: a marker of foetal and malignant epithelial cells of the human colon. Int. J. Cancer, 32: 407–412 (1983).

    Article  PubMed  CAS  Google Scholar 

  12. B. Lacroix, M. Kedinger, P. Simon-Assmann, M. Rousset, A. Zweibaum, and K. Haffen. Developmental pattern of brush border enzymes in the human fetal colon. Correlation with some morphogenetic events. Early Hum. Dev., 9: 95–103 (1984).

    Article  PubMed  CAS  Google Scholar 

  13. M. Rousset, E. Dussaulx, G. Chevalier, and A. Zweibaum, Expression phenotypique des antigènes coliques polymorphes (WZ) dans les adénocarcinomes du côlon humain. C.R. Acad. Sci. (Paris), 286: 659–662 (1978).

    CAS  Google Scholar 

  14. J. Bara, F. Loisillier, and P. Burtin, Antigens of gastric and intestinal mucous cells in human colonic tumours. Br. J. Cancer, 41: 209–221 (1980).

    Article  PubMed  CAS  Google Scholar 

  15. I. Chantret, A. Barbat, E. Dussaulx, M.G. Brattain, and A. Zweibaum, Epithelial polarity, villin expression and enterocytic differentiation of cultured human colon carcinoma cells: a survey of 20 cell lines. Cancer Res., 48: 1936–1942 (1988)

    PubMed  CAS  Google Scholar 

  16. J. Fogh, J.M. Fogh, and T. Orfeo, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J. Nati. Cancer Inst., 59: 221–225 (1977).

    CAS  Google Scholar 

  17. J. Fogh, and G. Trempe, New human tumor cell lines. In: Human Tumor Cells “In vitro”. Edited by J. Fogh, New York, Plenum Press, p. 115–141 (1975).

    Google Scholar 

  18. M. Pinto, S. Robine-Léon, M.D. Appay, M. Kedinger, N. Triadou, E. Dussaulx, B. Lacroix, P. Simon-Assmann, K. Haffen, J. Fogh, and A. Zweibaum, Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture. Biol. Cell., 47: 323–330 (1983).

    Google Scholar 

  19. M. Laburthe, M. Rousset, C. Rouyer-Fessard, A. Couvineau, I. Chantret, G. Chevalier, and A. Zweibaum, A. Development of vasoactive intestinal peptide-responsive adenylate cyclase during enterocytic differentiation of Caco-2 cells in culture: evidence for an increased receptor level. J. Biol. Chem., 262: 10180–10184 (1987).

    PubMed  CAS  Google Scholar 

  20. S. Robine, C. Huet, R. Moll, C. Sahuquillo-Merino, E. Coudrier, A. Zweibaum, and D. Louvard, Can villin be used to identify malignant and undifferentiated normal digestive epithelial cells?, Proc. Natl. Acad. Sci. USA, 82: 8488–8492 (1985).

    Article  PubMed  CAS  Google Scholar 

  21. A. Biais, P. Bissonnette, and A. Bertheloot, Common characteristics for Na+-dependent sugar transport in Caco-2 cells and human fetal colon. J. Membrane Biol., 99: 113–125 (1987).

    Article  Google Scholar 

  22. M. Laburthe, M. Rousset, G. Chevalier, C. Boissard, C. Dupont, A. Zweibaum, and G. Rosselin, Vasoactive intestinal peptide control of cyclic adenosine 3′: 5′-monophosphate in seven human colorectal adenocarcinoma cell lines in culture. Cancer Res., 40: 2529–2533 (1980).

    PubMed  CAS  Google Scholar 

  23. T.E. Hugues, J.M. Ordouas, and E.J. Schaeffer, Regulation of intestinal apolipoprotein B synthesis and secretion by Caco-2 cells. Lack of fatty acid effects and control by intracellular calcium ion. J. Biol. Chem., 263: 3425–3431 (1988).

    Google Scholar 

  24. E. Grasset, J. Bernabeu, and M. Pinto, Epithelial properties of human colonic carcinoma cell line Caco-2: effect of secretagogues. Am. J. Physiol. 248 (Cell Physiol. 17): C410–C418 (1985).

    PubMed  CAS  Google Scholar 

  25. E. Grasset, M. Pinto, E. Dussaulx, A. Zweibaum, and J.F. Desjeux, Epithelial properties of human colonic carcinoma cell line Caco-2: electrical parameters. Am. J. Physiol. 247 (Cell Physiol. 16): C260–C267, 1984.

    PubMed  CAS  Google Scholar 

  26. H.P. Hauri, E.E. Sterchi, D. Bienz, J. Fransen, and A. Marwer, Expression and intracellular transport of microvillus membrane hydrolases in human intestinal epithelial cells. J. Cell Biol., 101: 838–851 (1985).

    Article  PubMed  CAS  Google Scholar 

  27. H.P. Hauri, Biogenesis and intracellular transport of intestinal brush border membrane hydrolases. Use of antibody probes and tissue culture. In: Subcellular Biochemistry, G.R. Harris ed., Plenum Press, p. 155-219 (1988).

    Google Scholar 

  28. M. Rousset, M. Laburthe, M. Pinto, G. Chevalier, C. Rouyer-Fessard, E. Dussaulx, G. Trugnan, N. Boige, J.L. Brun, and A. Zweibaum, Enterocytic differentiation and glucose utilization in the human colon tumor cell line Caco-2: modulation by forskolin. J. Cell. Physiol., 123: 377–385 (1985).

    Article  PubMed  CAS  Google Scholar 

  29. M. Rousset, I. Chantret, D. Darmoul, G. Trugnan, C. Sapin, F. Green, D. Swallow, and A. Zweibaum, Reversible forskolin-induced impairment of sucrase-isomaltase mRNA levels, biosynthesis and transport to the brush border membrane in Caco-2 cells. J. Cell. Physiol. (in press).

    Google Scholar 

  30. J.L. Gaillard, P. Berche, J. Mounier, S. Richard, and P. Sansonetti, In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect. Immun., 55: 2822–2829 (1987).

    PubMed  CAS  Google Scholar 

  31. M. Pinto, M.D. Appay, P. Simon-Assmann, G. Chevalier, N. Dracopoli, J. Fogh, and A. Zweibaum, Enterocytic differentiation of cultured human colon cancer cells by replacement of glucose by galactose in the medium. Biol. Cell., 44: 193–196 (1982).

    CAS  Google Scholar 

  32. A. Zweibaum, M. Pinto, G. Chevalier, E. Dussaulx, N. Triadou, B. Lacroix, K. Haffen, J.L. Brun, and M. Rousset, Enterocytic differentiation of a supopulation of the human colon tumor cell line HT-29 selected for growth in sugar-free medium and its inhibition by glucose. J. Cell. Physiol., 122: 21–29 (1985).

    Article  PubMed  CAS  Google Scholar 

  33. B.M. Wice, G. Trugnan, M. Pinto, M. Rousset, G. Chevalier, E. Dussaulx, B. Lacroix, and A. Zweibaum, The intracellular accumulation of UDP-N-acetylhexosamines is concomitant with the inability of human colon cancer cells to differentiate. J. Biol. Chem., 260: 139–146 (1985).

    PubMed  CAS  Google Scholar 

  34. C. Huet, C. Sahuquillo-Merino, E. Coudrier, and D. Louvard, Absorption and mucus-secreting subclones isolated from a multipotent intestinal cell line (HT-29) provide new models for cell polarity and terminal differentiation. J. Cell Biol., 105: 345–357 (1987).

    Article  PubMed  CAS  Google Scholar 

  35. O. Godefroy, C. Huet, L.A.C. Blair, C. Sahuquillo-Merino, and D. Louvard, Differentiation of a clone isolated from the HT-29 cell line: polarized distribution of histocompatibility antigens (HLA) and of transferrin receptors. Biol. Cell., 63: 41–55 (1988).

    PubMed  CAS  Google Scholar 

  36. Augeron, C., and C.L. Laboisse, Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Res., 44: 3961–3969 (1984).

    PubMed  CAS  Google Scholar 

  37. Augeron, C., J.J. Maoret, C.L. Laboisse, and E. Grasset, Permanently differentiated cell clones established from the human colonic adenocarcinoma cell line HT-29: possible models for the study of ion transport and mucus production. In: Ion-Gradient-Coupled Transport, Edited by F. Alvarado & C.H. Van Os, Amsterdam, Elsevier, (1989) (in press).

    Google Scholar 

  38. G. Trugnan, M. Rousset, I. Chantret, A. Barbat, and A. Zweibaum, The post-translational processing of sucrase-isomaltase in HT-29 cells is a function of their state of enterocytic differentiation. J. Cell. Biol., 104: 1199–1205 (1987).

    Article  PubMed  CAS  Google Scholar 

  39. W.E.W. Roediger, Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology, 83: 424–429 (1982).

    PubMed  CAS  Google Scholar 

  40. C. Denis, V. Mils, J.C. Murat, M. Rousset, M. Pinto, V. Trocheris, A. Zweibaum, and H. Paris, Evidence for development of gluconeogenesis in the HT-29 human colon adenocarcinoma cell line grown in a glucose-free medium. IRCS Med. Sci., 13: 898–899 (1985).

    CAS  Google Scholar 

  41. E. Pringault, M. Arpin, A. Garcia, J. Finidori, and D. Louvard, A human villin cDNA clone to investigate the differentiation of intestinal and kidney cells in vivo and in culture. EMBO J., 5: 3119–3124 (1986).

    PubMed  CAS  Google Scholar 

  42. Laburthe, M. Rousset, C. Boissard, G. Chevalier, A. Zweibaum, and G. Rosselin, Vasoactive intestinal peptide: a potent stimulator of adenosine 3′: 5′-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. Proc. Natl. Acad. Sci. USA, 75: 2772–2775 (1978).

    Article  PubMed  CAS  Google Scholar 

  43. A. Couvineau, M. Rousset, and M. Laburthe, Molecular identification and structural requirement of vasoactive intestinal peptide (VIP) receptors in the human colon adenocarcinoma cell line, HT-29. Biochem. J., 231: 139–143 (1985).

    PubMed  CAS  Google Scholar 

  44. M. Laburthe, C. Augeron, C. Rouyer-Fessard, I. Roumagnac, J.J. Maoret, E. Grasset, and C. Laboisse, Functional VIP receptors in the human mucus-secreting colonic cell line C1.16E. Am. J. Physiol. (Gastrointest. Liver Physiol. 19): G443–G450 (1989).

    Google Scholar 

  45. P. Kitabgi, C. Poustis, C. Granier, J. Van Rietschoten, J. Rivier, J.L. Morgat, and P. Freychet, Neurotensin binding to extraneural and neural receptors: comparison with biological activity and structure-activity relationships. Mol. Pharmacol., 18: 11–19 (1980).

    PubMed  CAS  Google Scholar 

  46. P. Kitabgi, C. Poustis, A. Zweibaum, and P. Freychet, Peptide receptors in colonic tumor cells: specific binding of epidermal growth factor to the HT-29 cell line. In: Hormone Receptors in Digestion and Nutrition. Ed. by G. Rosselin, P. Fromageot & S. Bonfils, Elsevier/North Holland Biomedicai Press, p. 255-260 (1979).

    Google Scholar 

  47. H. Paris, B. Bouscarel, C. Cortinovis, and J.C. Murat, Growth-related variation of alpha2-adrenergic receptivity in the HT-29 adenocarcinoma cell line from human colon. FEBS Lett., 184: 82–86 (1985).

    Article  PubMed  CAS  Google Scholar 

  48. P. Simon-Assmann, F, Bouziges, D. Daviaud, K. Haffen, and M. Kedinger, Synthesis of glycosaminoglycans by undifferentiated and differentiated HT-29 human colonic cancer cells. Cancer Res., 47: 4478–4484 (1987).

    PubMed  CAS  Google Scholar 

  49. B.J. Siddiqui, J. Byrd, F.J. Fearney, and Y.S. Kim, Comparison of metabolically labelled mucins of LS-174T human colon cancer cells in tissue culture and xenograft. Tumor Biology (1989) (in press).

    Google Scholar 

  50. H. Murakami, and H. Masui, Hormonal control of human colon carcinoma cell growth in serum-free medium. Proc. Natl. Acad. Sci. USA, 77: 3464–3468 (1980).

    Article  PubMed  CAS  Google Scholar 

  51. K. Dharmsathaphorn, K.G. Mandel, H. Masui, and J.A. McRoberts, VIP-induced chloride secretion by a colonic epithelial cell line: direct participation of a basolaterally localized Na+, K+, Cl− cotransport system. J. Clin. Invest., 75: 462–471 (1985).

    Article  PubMed  CAS  Google Scholar 

  52. K. Dharmsathaphorn, K.G. Mandel, J.A. McRoberts, C.A. Cartwright, and H. Masui, Utilization of a human colonic tumor cell line as a model to study electrolyte transport in the intestine. In: Intestinal Absorption and Secretion (Falk Symp. No 36) Ed. by E. Skadhauge & K. Heintze, Lancaster: MTP, p. 325–333 (1984).

    Google Scholar 

  53. K. Dharmsathaphorn, K.G. Mandel, J.A. McRoberts, L.D. Tisdale, and H. Masui, A human colonic tumor cell line that maintains vectorial electrolyte transport. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G204–G208 (1984).

    PubMed  CAS  Google Scholar 

  54. A. Weymer, P. Huott, W. Liu, J.A. McRoberts, and K. Dharmsathaphorn, Chloride secretory mechanism induced by prostaglandin E1 in a colonic epithelial cell line. J. Clin. Invest., 76: 1828–1836 (1985).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unité de Recherches sur la Différenciation et la Neuroendocrinologie de Cellules Digestives (INSERM U178), 16 avenue Paul Vaillant Couturier, 94807, Villejuif Cedex, France

    Alain Zweibaum

Authors
  1. Alain Zweibaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA

    Glynn Wilson

  2. University of Nottingham, Nottingham, UK

    S. S. Davis  & L. Illum  & 

  3. INSERM, Paris, France

    Alain Zweibaum

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Plenum Press, New York

About this chapter

Cite this chapter

Zweibaum, A. (1991). Differentiation of Human Colon Cancer Cells. In: Wilson, G., Davis, S.S., Illum, L., Zweibaum, A. (eds) Pharmaceutical Applications of Cell and Tissue Culture to Drug Transport. NATO ASI Series, vol 218. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0286-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-0286-6_3

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-0288-0

  • Online ISBN: 978-1-4757-0286-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation