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N-cadherin involvement in the heterotypic adherence of malignant T-cells to epithelia

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Abstract

N-cadherin, a cell adhesion molecule normally found in neural cell tissue, has been found recently to be expressed on the surface of malignant T-cells. The function of N-cadherin on these cells remains unclear. Heterotypic assays between Molt-3 T lymphoblastic leukemia cells and Caco-2 epithelial monolayers were examined under different conditions to assess the functional role of N-cadherin. The results indicate that adherence of Molt-3 cells to Caco-2 monolayers was reduced significantly following pretreatment of Molt-3 cells with 100 μM of an N-cadherin-derived antagonist decapeptide. In contrast, pretreatment of Molt-3 cells with an anti-N-cadherin antibody raised against the first 20 amino acids of N-cadherin sequence led to a surprisingly marked enhancement of Molt-3 cell adherence to Caco-2 monolayers. In addition, the presence of anti-N-cadherin antibody neutralized the inhibitory effect of anti-ICAM-1 on Molt-3 adhesion to Caco-2 monolayers. This novel finding demonstrates that external stimulus through the N-cadherin amino terminus can modulate adhesion of malignant T-cells to epithelia and may promote their ability to invade or metastasize to inflammatory sites.

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References

  1. Takeichi M: Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251: 1451–1455, 1991

    Google Scholar 

  2. Brieher WM, Yap AS, Gumbiner BM: Lateral dimerization is required for the homophilic binding activity of C-cadherin. J Cell Biol 135: 487–496, 1996

    Google Scholar 

  3. Tanaka H, Shan W, Phillips GR, Arndt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR: Molecular modification of Ncadherin in response to synaptic activity. Neuron 25: 93–107, 2000

    Google Scholar 

  4. Tang A, Amagai M, Granger LG, Stanley JR, Udey MC: Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361: 82–85, 1993

    Google Scholar 

  5. Lee MG, Sharrow SO, Farr AG, Singer A, Udey MC: Expression of the homotypic adhesion molecule E-cadherin by immature murine thymocytes and thymic epithelial cells. J Immunol 152: 5653–5659, 1994

    Google Scholar 

  6. Higgins JM, Cernadas M, Tan K, Irie A, Wang J, Takada Y, Brenner MB: The role of α and β chains in ligand recognition by β7 integrins. J Biol Chem 275: 25652–25664, 2000

    Google Scholar 

  7. Taraszka KS, Higgins JM, Tan K, Mandelbrot DA, Wang JH, Brenner MB: Molecular basis for leukocyte integrin αE β7 adhesion to epithelial E-cadherin. J Exp Med 191: 1555–1567, 2000

    Google Scholar 

  8. Agace WW, Higgins JM, Sadasivan B, Brenner MB, Parker CM: Tlymphocyte-epithelial-cell interactions: integrin αE β7, LEEP-CAM and chemokines. Curr Opin Cell Biol 12: 563–568, 2000

    Google Scholar 

  9. Tsutsui J, Moriyama M, Arima N, Ohtsubo H, Tanaka H, Ozawa M: Expression of cadherin-catenin complexes in human leukemia cell lines. J Biochem (Tokyo) 120: 1034–1039, 1996

    Google Scholar 

  10. Matsuyoshi N, Toda K, Imamura S: N-cadherin expression in human adult T-cell leukemia cell line. Arch Dermatol Res 290: 223–225, 1998

    Google Scholar 

  11. Kawamura-Kodama K, Tsutsui J, Suzuki ST, Kanzaki T, Ozawa M: Ncadherin expressed on malignant T cell lymphoma cells is functional, and promotes heterotypic adhesion between the lymphoma cells and mesenchymal cells expressing N-cadherin. J Invest Dermatol 112: 62–66, 1999

    Google Scholar 

  12. Kaiserlian D, Rigal D, Abello J, Revillard JP: Expression, function and regulation of the intercellular adhesion molecule-1 (ICAM-1) on human intestinal epithelial cell lines. Eur J Immunol 21: 2415–2421, 1991

    Google Scholar 

  13. Yusuf-Makagiansar H, Makagiansar IT, Siahaan TJ: Inhibition of the adherence of T-lymphocytes to epithelial cells by a cyclic peptide derived from inserted domain of lymphocyte function-associated antigen-1. Inflammation 25: 203–214, 2001

    Google Scholar 

  14. Huang C, Springer TA: A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1). J Biol Chem 270: 19008–19016, 1995

    Google Scholar 

  15. Williams E, Williams G, Gour BJ, Blaschuk OW, Doherty P: J Biol Chem 275: A novel family of cyclic peptide antagonists suggests that N-cadherin specificity is determined by amino acids that flank the HAV motif. J Biol Chem 275: 4007–4012, 2000

    Google Scholar 

  16. Pertz O, Bozic D, Koch AW, Fauser C, Brancaccio A, Engel J: A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation. EMBO J 18: 1738–1747, 1999

    Google Scholar 

  17. Hirano S, Kimoto N, Shimoyama Y, Hirohashi S, Takeichi M: Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell 70: 293–301, 1992

    Google Scholar 

  18. Hulsken J, Birchmeier W, Behrens J: E-cadherin and APC compete for the interaction with β-catenin and the cytoskeleton. J Cell Biol 127: 2061–2069, 1994

    Google Scholar 

  19. Uchida N, Honjo Y, Johnson KR, Wheelock MJ, Takeichi M: The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones. J Cell Biol 135: 767–779, 1996

    Google Scholar 

  20. Islam S, Carey TE, Wolf GT, Wheelock MJ, Johnson KR: Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion. J Cell Biol 135: 1643–1654, 1996

    Google Scholar 

  21. Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA: Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 148: 779–790, 2000

    Google Scholar 

  22. Ross L, Hassman F, Molony L. Inhibition of Molt-4-endothelial adherence by synthetic peptides from the sequence of ICAM-1. J Biol Chem 267: 8537–8543, 1992

    Google Scholar 

  23. Hong RL, Pu YS, Chu JS, Lee WJ, Chen YC, Wu CW: Correlation of expression of CD44 isoforms and E-cadherin with differentiation in human urothelial cell lines and transitional cell carcinoma. Cancer Lett 89:81–87, 1995

    Google Scholar 

  24. Stewart AO, Bhatia PA, McCarty CM, Patel MV, Staeger MA, Arendsen DL, Gunawardana IW, Melcher LM, Zhu GD, Boyd SA, Fry DG, Cool BL, Kifle L, Lartey K, Marsh KC, Kempf-Grote AJ, Kilgannon P, Wisdom W, Meyer J, Gallatin WM, Okasinski GF: Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. Selective inhibition of ICAM-1 and E-selectin expression. J Med Chem 44: 988–1002, 2001

    Google Scholar 

  25. Kitagawa M, Natori M, Murase S, Hirano S, Taketani S, Suzuki ST: Mutation analysis of cadherin-4 reveals amino acid residues of EC1 important for the structure and function. Biochem Biophys Res Commun 271: 358–363, 2000

    Google Scholar 

  26. Shapiro L, Fannon AM, Kwong PD, Thompson A, Lehmann MS, Grubel G, Legrand JF, Als-Nielsen J, Colman DR, Hendrickson WA: Structural basis of cell-cell adhesion by cadherins. Nature 374: 327–337, 1995

    Google Scholar 

  27. Tamura K, Shan WS, Hendrickson WA, Colman DR, Shapiro L: Structure-function analysis of cell adhesion by neural N-cadherin. Neuron 20: 1153–1163, 1998

    Google Scholar 

  28. Blaschuk OW, Sullivan R, David S, Pouliot Y: Identification of a cadherin cell adhesion recognition sequence. Dev Biol 139: 227–229, 1990

    Google Scholar 

  29. Halama T, Groger M, Pillinger M, Staffler G, Prager E, Stockinger H, Holnthoner W, Lechleitner S, Wolff K, Petzelbauer P: Platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin cooperatively regulate fibroblast growth factor-induced modulations of adherens junction functions. J Invest Dermatol 116: 110–117, 2001

    Google Scholar 

  30. Kallakury BV, Sheehan CE, Ross JS: Co-downregulation of cell adhesion proteins α-and β-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. Hum Pathol 32: 849–855, 2001

    Google Scholar 

  31. Molema G, Cohen Tervaert JW, Kroesen BJ, Helfrich W, Meijer DK, de Leij LF: CD3 directed bispecific antibodies induce increased lymphocyte-endothelial cell interactions in vitro. Br J Cancer 82: 472–479, 2000

    Google Scholar 

  32. Molema G, Kroesen BJ, Helfrich W, Meijer DK, de Leij LF: The use of bispecific antibodies in tumor cell and tumor vasculature directed immunotherapy. J Control Release 64: 229–239, 2000

    Google Scholar 

  33. Mariadason JM, Bordonaro M, Aslam F, Shi L, Kuraguchi M, Velcich A, Augenlicht LH: Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Res 61: 3465–3471, 2001

    Google Scholar 

  34. McEwen DG, Peifer M: Wnt signaling: Moving in a new direction. Curr Biol 10: R562–R564, 2000

    Google Scholar 

  35. Makagiansar IT, Sinaga E, Calcagno AM, Xu CR, Siahaan TJ: Roles of E-cadherin and β-catenin in cell adhesion, signaling and possible therapeutic applications. Curr Top Biochem Res 2: 51–61, 2000

    Google Scholar 

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Makagiansar, I.T., Yusuf-Makagiansar, H., Ikesue, A. et al. N-cadherin involvement in the heterotypic adherence of malignant T-cells to epithelia. Mol Cell Biochem 233, 1–8 (2002). https://doi.org/10.1023/A:1015556625038

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  • DOI: https://doi.org/10.1023/A:1015556625038

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