Kaohsiung Journal of Medical Sciences
Volume 24, Issue 11 , Pages 577-590, November 2008

Differential CCR4 Expression And Function in Cutaneous T-Cell Lymphoma Cell Lines

  • Chieh-Shan Wu

      Affiliations

    • Department of Dermatology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taichung, Taiwan
  • ,
  • Sin-Ting Wang

      Affiliations

    • Department of Dermatology, China Medical University, Taichung, Taiwan
  • ,
  • Chai-Yu Liao

      Affiliations

    • Department of Dermatology, China Medical University, Taichung, Taiwan
  • ,
  • Meng-Tse Wu

      Affiliations

    • Department of Dermatology, China Medical University, Taichung, Taiwan
    • Corresponding Author InformationAddress correspondence and reprint requests to: Dr Meng-Tse Wu, Department of Dermatology, China Medical University, 2 Yuh Der Road, Taichung 404, Taiwan

Received 9 September 2008; accepted 18 November 2008.

Article Outline

Cutaneous T cell lymphoma (CTCL) is a clonal epidermotropic malignancy of memory T cells primarily involving the skin. However, the mechanisms governing migration of CTCL cells have not been fully clarified. It has been shown that certain chemokine receptors are upregulated in CTCL cells, but it remains unanswered whether these chemokine receptors play a critical role in the migration dynamics of CTCL. Using cell lines originally derived from patients with different subtypes of CTCL, we have shown higher CCR4 expression in the line derived from the mycosis fungoides (MJ), compared with the line derived from Sézary syndrome (Hut78). In specific responses to CCL22 (a CCR4 ligand) treatments, MJ cells showed significant chemotactic migration, enhanced activation and adhesion of certain integrins (CD49d and CD29) in vitro, while the control cells (Hut78, CD4+CD45RO+ memory T cells, and Jurkat cells) did not. Furthermore, compared with Hut78 cells, MJ cells manifested significantly more transendothelial migration in responses to treatments with either CCL22 or conditioned medium from dendritic cells in vitro. These results provide further dynamic evidence, in line with the multistep cascade paradigm for leukocyte transendothelial migration, to support a critical role for CCR4 in CTCL migration.

Key Words:  CCR4 , chemokine , cutaneous T-cell lymphoma

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References 

  1. Willemze R , Jaffe ES , Burg G , et al.   WHO-EORTC classification for cutaneous lymphomas . Blood . 2005;105:3768–3785
  2. Robert C , Kupper TS . Inflammatory skin diseases, T cells, and immune surveillance . N Engl J Med . 1999;341:1817–1828
  3. Zollner TM , Asadullah K , Schon MP . Targeting leukocyte trafficking to inflamed skin: still an attractive therapeutic approach? . Exp Dermatol . 2007;16:1–12
  4. Kakinuma T , Nakamura K , Wakugawa M , et al.   Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely related with disease activity . J Allergy Clin Immunol . 2001;107:535–541
  5. Heald PW , Yan SL , Edelson RL , et al.   Skin-selective lymphocyte homing mechanisms in the pathogenesis of leukemic cutaneous T-cell lymphoma . J Invest Dermatol . 1993;101:222–226
  6. Shiohara T , Moriya N , Gotoh C , et al.   Differential expression of lymphocyte function-associated antigen 1 (LFA-1) on epidermotropic and non-epidermotropic T-cell clones . J Invest Dermatol . 1989;93:804–808
  7. Hwang ST , Fitzhugh DJ . Aberrant expression of adhesion molecules by Sezary cells: functional consequences under physiologic shear stress conditions . J Invest Dermatol . 2001;116:466–470
  8. Kallinich T , Muche JM , Qin S , et al.   Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides . J Invest Dermatol . 2003;121:1045–1052
  9. Kakinuma T , Sugaya M , Nakamura K , et al.   Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides . J Am Acad Dermatol . 2003;48:23–30
  10. Starkebaum G , Loughran TP , Waters CA , et al . Establishment of an IL-2 independent, human T-cell line possessing only the p70 IL-2 receptor . Int J Cancer . 1991;49:246–253
  11. Gootenberg JE , Ruscetti FW , Mier JW , et al.   Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor . J Exp Med . 1981;154:1403–1418
  12. Popovic M , Sarin PS , Robert-Gurroff M , et al.   Isolation and transmission of human retrovirus (human t-cell leukemia virus) . Science . 1983;219:856–859
  13. Weiss A , Wiskocil RL , Stobo JD . The role of T3 surface molecules in the activation of human T cells: a twostimulus requirement for IL 2 production reflects events occurring at a pre-translational level . J Immunol . 1984;133:123–128
  14. Wiley HE , Gonzalez EB , Maki W , et al.   Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma . J Natl Cancer Inst . 2001;93:1638–1643
  15. Wu MT , Hwang ST . CXCR5-transduced bone marrowderived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses . J Immunol . 2002;168:5096–5102
  16. Notohamiprodjo M , Segerer S , Huss R , et al.   CCR10 is expressed in cutaneous T-cell lymphoma . Int J Cancer . 2005;115:641–647
  17. Shamri R , Grabovsky V , Gauguet JM , et al.   Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines . Nat Immunol . 2005;6:497–506
  18. Wu M , Fang H , Hwang ST . Cutting edge: CCR4 mediates antigen-primed T cell binding to activated dendritic cells . J Immunol . 2001;167:4791–4795
  19. Rose DM , Cardarelli PM , Cobb RR , Ginsberg MH . Soluble VCAM-1 binding to alpha4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells . Blood . 2000;95:602–609
  20. Garcia-Bernal D , Wright N , Sotillo-Mallo E , et al.   Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the integrin alpha 4 beta 1 . Mol Biol Cell . 2005;16:3223–3235
  21. Chan JR , Hyduk SJ , Cybulsky MI . Alpha 4 beta 1 integrin/VCAM-1 interaction activates alpha L beta 2 integrin-mediated adhesion to ICAM-1 in human T cells . J Immunol . 2000;164:746–753
  22. Ades EW , Candal FJ , Swerlick RA , et al.   HMEC-1: establishment of an immortalized human microvascular endothelial cell line . J Invest Dermatol . 1992;99:683–690
  23. Till KJ , Lin K , Zuzel M , et al.   The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes . Blood . 2002;99:2977–2984
  24. Arroyo AG , Sanchez-Mateos P , Campanero MR , et al.   Regulation of the VLA integrin-ligand interactions through the beta 1 subunit . J Cell Biol . 1992;117:659–670
  25. Chan JR , Hyduk SJ , Cybulsky MI . Chemoattractants induce a rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular cell adhesion molecule 1 which mediates arrest: an early step in the process of emigration . J Exp Med . 2001;193:1149–1158
  26. Ferenczi K , Fuhlbrigge RC , Pinkus J , et al.   Increased CCR4 expression in cutaneous T cell lymphoma . J Invest Dermatol . 2002;119:1405–1410
  27. Katou F , Ohtani H , Nakayama T , et al.   Macrophagederived chemokine (MDC/CCL22) and CCR4 are involved in the formation of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary lymphoid tissue . Am J Pathol . 2001;158:1263–1270
  28. Baggiolini M . Chemokines in pathology and medicine . J Intern Med . 2001;250:91–104
  29. Chen GS , Yu HS , Lan CC , et al.   CXC chemokine receptor CXCR4 expression enhances tumorigenesis and angiogenesis of basal cell carcinoma . Br J Dermatol . 2006;154:910–918
  30. Saeki H , Tamaki K . Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases . J Dermatol Sci . 2006;43:75–84
  31. D'Ambrosio D , Albanesi C , Lang R , et al.   Quantitative differences in chemokine receptor engagement generate diversity in integrin-dependent lymphocyte adhesion . J Immunol . 2002;169:2303–2312
  32. Mariani M , Lang R , Binda E , et al.   Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4 desensitization and internalization on human Th2 cells . Eur J Immunol . 2004;34:231–240
  33. Curiel TJ , Coukos G , Zou L , et al.   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival . Nat Med . 2004;10:942–949
  34. Cronshaw DG , Owen C , Brown Z , et al.   Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis . J Immunol . 2004;172:7761–7770
  35. Girardi M , Heald PW , Wilson LD . The pathogenesis of mycosis fungoides . N Engl J Med . 2004;350:1978–1988
  36. Berger CL , Hanlon D , Kanada D , et al.   The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells . Blood . 2002;99:2929–2939
  37. Berger CL , Tigelaar R , Cohen J , et al.   Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells . Blood . 2005;105:1640–1647
  38. Kinashi T . Intracellular signalling controlling integrin activation in lymphocytes . Nat Rev Immunol . 2005;5:546–559
  39. Schechner JS , Edelson RL , McNiff JM , et al.   Integrins alpha 4 beta 7 and alpha E beta 7 are expressed on epidermotropic T cells in cutaneous T cell lymphoma and spongiotic dermatitis . Lab Invest . 1999;79:601–607
  40. Laudanna C , Alon R . Right on the spot. Chemokine triggering of integrin-mediated arrest of rolling leukocytes . Thromb Haemost . 2006;95:5–11
  41. Narducci MG , Scala E , Bresin A , et al.   Skin homing of Sezary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV . Blood . 2006;107:1108–1115
  42. Ishida T , Ueda R . CCR4 as a novel molecular target for immunotherapy of cancer . Cancer Sci . 2006;97:1139–1146

PII: S1607-551X(09)70019-1

doi:10.1016/S1607-551X(09)70019-1

Kaohsiung Journal of Medical Sciences
Volume 24, Issue 11 , Pages 577-590, November 2008