Gastroenterology
Volume 132, Issue 2 , Pages 587-600 , February 2007

Cell-Cell Contacts Prevent Anoikis in Primary Human Colonic Epithelial Cells

  • Claudia Hofmann

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Florian Obermeier

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Monika Artinger

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Martin Hausmann

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Werner Falk

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Juergen Schoelmerich

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • ,
  • Gerhard Rogler

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • Corresponding Author InformationAddress requests for reprints to: Gerhard Rogler, MD, PhD, Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany. fax: (49) 941-944-7179.
    • ,
  • Johannes Grossmann

      Affiliations

    • Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
    • Department of Medicine, Bethesda Hospital, Mönchengladbach, Germany

Received 12 September 2005 ,Accepted 26 October 2006.

References 

  1. Gavrieli Y, Sherman Y, Ben Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992;119:493–501
  2. Grossmann J, Walther K, Artinger M, Rummele P, Woenckhaus M, Scholmerich J. Induction of apoptosis before shedding of human intestinal epithelial cells. Am J Gastroenterol. 2002;97:1421–1428
  3. Potten CS, Allen TD. Ultrastructure of cell loss in intestinal mucosa. J Ultrastruct Res. 1977;60:272–277
  4. Strater J, Koretz K, Gunthert AR, Moller P. In situ detection of enterocytic apoptosis in normal colonic mucosa and in familial adenomatous polyposis. Gut. 1995;37:819–825
  5. Grossmann J. Molecular mechanisms of “detachment-induced apoptosis—anoikis.”. Apoptosis. 2002;7:247–260
  6. Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124:619–626
  7. Beaulieu JF. Differential expression of the VLA family of integrins along the crypt-villus axis in the human small intestine. J Cell Sci. 1992;102:427–436
  8. Gordon JI, Hermiston ML. Differentiation and self-renewal in the mouse gastrointestinal epithelium. Curr Opin Cell Biol. 1994;6:795–803
  9. Koretz K, Schlag P, Boumsell L, Moller P. Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol. 1991;138:741–750
  10. Probstmeier R, Martini R, Schachner M. Expression of J1/tenascin in the crypt-villus unit of adult mouse small intestine: implications for its role in epithelial cell shedding. Development. 1990;109:313–321
  11. Riedl S, Moller P, Faissner A, Schlag P. Induction and altered distribution of tenascin in the basal lamina of colorectal adenomas and carcinomas. EXS. 1992;61:277–281
  12. Zutter MM, Santoro SA. Widespread histologic distribution of the alpha 2 beta 1 integrin cell-surface collagen receptor. Am J Pathol. 1990;137:113–120
  13. Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996;87:171
  14. Cohen GM. Caspases: the executioners of apoptosis. Biochem J. 1997;326:1–16
  15. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem. 1999;68:383–424
  16. Salvesen GS, Dixit VM. Caspases: intracellular signaling by proteolysis. Cell. 1997;91:443–446
  17. Thornberry NA. Caspases: key mediators of apoptosis. Chem Biol. 1998;5:R97–R103
  18. Grossmann J, Walther K, Artinger M, Kiessling S, Scholmerich J. Apoptotic signaling during initiation of detachment-induced apoptosis (“anoikis”) of primary human intestinal epithelial cells. Cell Growth Differ. 2001;12:147–155
  19. Susin SA, Zamzami N, Castedo M, Daugas E, Wang HG, Geley S, et al. The central executioner of apoptosis: multiple connections between protease activation and mitochondria in Fas/APO-1/. J Exp Med. 1997;186:25–37
  20. Gumbiner BM. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996;84:345–357
  21. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993;9:317–321
  22. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991;251:1451–1455
  23. Giancotti FG, Ruoslahti E. Integrin signaling. Science. 1999;285:1028–1032
  24. Zhan M, Zhao H, Han ZC. Signalling mechanisms of anoikis. Histol Histopathol. 2004;19:973–983
  25. Grossmann J, Maxson JM, Whitacre CM, Orosz DE, Berger NA, Fiocchi C, et al. New isolation technique to study apoptosis in human intestinal epithelial cells. Am J Pathol. 1998;153:53–62
  26. Grossmann J, Walther K, Artinger M, Kiessling S, Steinkamp M, Schmautz WK, et al. Progress on isolation and short-term ex-vivo culture of highly purified non-apoptotic human intestinal epithelial cells (IEC). Eur J Cell Biol. 2003;82:262–270
  27. Rogler G, Daig R, Aschenbrenner E, Vogl D, Schlottmann K, Falk W, et al. Establishment of long-term primary cultures of human small and large intestinal epithelial cells. Lab Invest. 1998;78:889–890
  28. Aberle H, Schwartz H, Kemler R. Cadherin-catenin complex: protein interactions and their implications for cadherin function. J Cell Biochem. 1996;61:514–523
  29. Ozawa M, Kemler R. Molecular organization of the uvomorulin-catenin complex. J Cell Biol. 1992;116:989–996
  30. Hermiston ML, Gordon JI. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J Cell Biol. 1995;129:489–506
  31. Hermiston ML, Gordon JI. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 1995;270:1203–1207
  32. Bergin E, Levine JS, Koh JS, Lieberthal W. Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism. Am J Physiol Renal Physiol. 2000;278:F758–F768
  33. Fouquet S, Lugo-Martinez VH, Faussat AM, Renaud F, Cardot P, Chambaz J, et al. Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes. J Biol Chem. 2004;279:43061–43069
  34. Kantak SS, Kramer RH. E-cadherin regulates anchorage-independent growth and survival in oral squamous cell carcinoma cells. J Biol Chem. 1998;273:16953–16961
  35. Laprise P, Chailler P, Houde M, Beaulieu JF, Boucher MJ, Rivard N. Phosphatidylinositol 3-kinase controls human intestinal epithelial cell differentiation by promoting adherens junction assembly and p38 MAPK activation. J Biol Chem. 2002;277:8226–8234
  36. Downward J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol. 1998;10:262–267
  37. Kulik G, Klippel A, Weber MJ. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol. 1997;17:1595–1606
  38. Marte BM, Downward J. PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci. 1997;22:355–358
  39. Murga C, Laguinge L, Wetzker R, Cuadrado A, Gutkind JS. Activation of Akt/protein kinase B by G protein-coupled receptors (A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through phosphatidylinositol-3-OH kinasegamma). J Biol Chem. 1998;273:19080–19085
  40. Scheid MP, Woodgett JR. Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 2003;546:108–112
  41. Pece S, Chiariello M, Murga C, Gutkind JS. Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions (Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex). J Biol Chem. 1999;274:19347–19351
  42. Pang JH, Kraemer A, Stehbens SJ, Frame MC, Yap AS. Recruitment of phosphoinositide 3-kinase defines a positive contribution of tyrosine kinase signaling to E-cadherin function. J Biol Chem. 2005;280:3043–3050
  43. Maldonado RA, Irvine DJ, Schreiber R, Glimcher LH. A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature. 2004;431:527–532
  44. Grossmann J, Mohr S, Lapentina EG, Fiocchi C, Levine AD. Sequential and rapid activation of select caspases during apoptosis of normal intestinal epithelial cells. Am J Physiol. 1998;274:G1117–G1124
  45. Sambrook J, Fritsch EF, Maniatis T. Commonly used techniques in molecular cloning. molecular cloning. 3rd ed.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory; 1989;E3–E11
  46. Grossmann J, Artinger M, Grasso AW, Kung HJ, Scholmerich J, Fiocchi C, et al. Hierarchical cleavage of focal adhesion kinase by caspases alters signal transduction during apoptosis of intestinal epithelial cells. Gastroenterology. 2001;120:79–88
  47. Jost M, Huggett TM, Kari C, Rodeck U. Matrix-independent survival of human keratinocytes through an EGF receptor/MAPK-kinase-dependent pathway. Mol Biol Cell. 2001;12:1519–1527
  48. Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J. 1997;16:2783–2793
  49. Pece S, Gutkind JS. Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation. J Biol Chem. 2000;275:41227–41233
  50. Shen X, Kramer RH. Adhesion-mediated squamous cell carcinoma survival through ligand-independent activation of epidermal growth factor receptor. Am J Pathol. 2004;165:1315–1329
  51. Loza-Coll MA, Perera S, Shi W, Filmus J. A transient increase in the activity of Src-family kinases induced by cell detachment delays anoikis of intestinal epithelial cells. Oncogene. 2005;24:1727–1737
  52. Windham TC, Parikh NU, Siwak DR, Summy JM, McConkey DJ, Kraker AJ, et al. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002;21:7797–7807
  53. Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol. 1996;134:793–799
  54. Anderson P. Kinase cascades regulating entry into apoptosis. Microbiol Mol Biol Rev. 1997;61:33–46
  55. Lavin MF, Watters D, Song Q. Role of protein kinase activity in apoptosis. Experientia. 1996;52:979–994
  56. Peluso JJ, Pappalardo A, Fernandez G. E-cadherin-mediated cell contact prevents apoptosis of spontaneously immortalized granulosa cells by regulating Akt kinase activity. Biol Reprod. 2001;64:1183–1190
  57. McFall A, Ulku A, Lambert QT, Kusa A, Rogers-Graham K, Der CJ. Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase. Mol Cell Biol. 2001;21:5488–5499
  58. Tsukita S, Oishi K, Akiyama T, Yamanashi Y, Yamamoto T, Tsukita S. Specific proto-oncogenic tyrosine kinases of src family are enriched in cell-to-cell adherens junctions where the level of tyrosine phosphorylation is elevated. J Cell Biol. 1991;113:867–879
  59. Defilippi P, Bozzo C, Volpe G, Romano G, Venturino M, Silengo L, et al. Integrin-mediated signal transduction in human endothelial cells: analysis of tyrosine phosphorylation events. Cell Adhes Commun. 1994;2:75–86
  60. Steinhusen U, Badock V, Bauer A, Behrens J, Wittman-Liebold B, Dorken B, et al. Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential. J Biol Chem. 2000;275:16345–16353
  61. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 1997;16:3797–3804
  62. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303:1483–1487
  63. Hagiwara C, Tanaka M, Kudo H. Increase in colorectal epithelial apoptotic cells in patients with ulcerative colitis ultimately requiring surgery. J Gastroenterol Hepatol. 2002;17:758–764
  64. Marini M, Bamias G, Rivera-Nieves J, Moskaluk CA, Hoang SB, Ross WG, et al. TNF-alpha neutralization ameliorates the severity of murine Crohn’s-like ileitis by abrogation of intestinal epithelial cell apoptosis. Proc Natl Acad Sci U S A. 2003;100:8366–8371
  65. Strater J, Wellisch I, Riedl S, Walczak H, Koretz K, Tandara A, et al. CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology. 1997;113:160–167
  66. Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach A, Obermuller N, et al. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol Gastrointest Liver Physiol. 2001;281:G216–G228
  67. Marin ML, Greenstein AJ, Geller SA, Gordon RE, Aufses AH. A freeze fracture study of Crohn’s disease of the terminal ileum: changes in epithelial tight junction organization. Am J Gastroenterol. 1983;78:537–547
  68. Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, et al. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999;116:301–309
  69. Louis E, Ribbens C, Godon A, Franchimont D, De Groote D, Hardy N, et al. Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease. Clin Exp Immunol. 2000;120:241–246
  70. von Lampe B, Barthel B, Coupland SE, Riecken EO, Rosewicz S. Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut. 2000;47:63–73
  71. Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430:1034–1039

 Supported by the Deutsche Forschungsgemeinschaft (SFB 585) and DFG grant OB 135/8-1 (to F.O.) and RO 1236/13-1 (to G.R.).

PII: S0016-5085(06)02472-3

doi: 10.1053/j.gastro.2006.11.017

Gastroenterology
Volume 132, Issue 2 , Pages 587-600 , February 2007

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