Effects Of Activation Of CD30 Signaling Pathway On CD30+ Cutaneous Anaplastic Large Cell Lymphoma Cell Lines

Year 2000, Volume: 1 Issue: 2, 33 - 37, 01.08.2000

Edi Levi Walther M. Pfeıfer Marshall E. Kadın

Abstract

Aims: CD30 activation has pleiotropic effects on different cell lines representing CD30+ lymphomas. In nodal T-cell anaplastic large cell lymphomas (ALCL), CD30 activation causes cytolysis and decreased proliferation while in Hodgkin’s disease there is either no change or proliferation depending on the cell lines. Mac-1 and Mac-2A are two clonally related cutaneous CD30+ anaplastic large cell lymphoma cell lines developed from early (Mac-1) and advanced (Mac-2A) disease from the same patient. Mac-1 is sensitive to transforming growth factor-b (TGF-b) mediated growth inhibition while Mac-2A is resistant. Both cell lines secrete an activated form of TGF-?. Our aim was to investigate the effects of CD30 activation on Mac cell lines. Methods: To understand the effects of CD30 activation, Mac cell lines were incubated with a CD30 agonistic antibody (HeFi-1). H-thymidine incorporation, tumor necrosis factor receptor associated factor 1 (TRAF1) expression and nuclear factor-kB activity was determined. Results: Mac-1 and Mac-2A showed increased proliferation with HeFi-1 while the nodal ALCL cell lines were inhibited. When Mac-1 cells were incubated with HeFi-1 and TGF-b neutralizing antibody, the proliferative rate markedly increased compared to HeFi-1 only. TGF-b resistant cell line Mac-2A did not show the same increase Mac-1 and Mac-2A had activation of NF-kB binding activity and increased expression of TRAF1 in response to CD30 activation by HeFi-1. Significance: This is the first demonstration of functionality of the CD30 signaling pathway in cutaneous CD30+ ALCLs. Autocrine TGF-b secreted from Mac-1 cells partially inhibits the proliferative signal from CD30 activation. These results suggest that TGF-b may interact with the CD30 signaling pathway in the pathogenesis of cutaneous ALCL.

Keywords

CD30, anaplastic large cell lymphoma, NF-kB, TRAF1

References

• 1. Willemze R, Kerl H, Sterry W et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the EORTC. Blood 1997; 90: 354-71.
• 2. Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK. WHO classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Aprogress report. Am J Clin Path 1999; 111 (Suppl 1): S8-S12.
• 3. Paulli M, Berti E, Rosso R et al. CD30/Ki-1 positive lymphoproliferative disorders of the skin-clinicopathologic correlation and statistical analysis of 86 cases: A multicentric study from the European Organization for Research and Treatment of Cancer, Cutaneous Lymphoma Project Group. J Clin Oncol 1995; 13: 1343-54.
• 4. Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1) - positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol 1993; 28: 973-80.
• 5. Cabanillas F, Armitage J, Pugh WC et al. Lympensity to transform into malignant lymphoma. Ann Intern Med 1995; 122: 210-7.
• 6. Falini B, Pileri S, Pizzolo G et al. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood 1995; 85: 1-14.
• 7. Smith CA, Gruss HJ, Davis T, et al. CD30 antigen, a marker for Hodgkin’s lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF. Cell 1993; 73: 1349-60.
• 8. Amakawa R, Hakem A, Kundig TM, et al. Impaired negative selection of T cells in Hodgkin’s disease antigen CD30-deficient mice Cell 1996; 84: 551-62.
• 9. Gruss HJ, Boiani N, Williams DE et al. Pleiotropic effects of the CD30 ligand on CD30 expressing cells and lymphoma cell lines. Blood 1994; 83:2045- 56.
• 10. Lee SY, Park CG, Choi Y. T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors. J Exp Med 1996; 183: 669-74.
• 11. Davis TH, Morton CC, Miller-Cassman R et al. Hodgkin’s disease, lymphomatoid papulosis and cutaneous T cell lymphoma derived from a common T cell clone. N Eng J Med 1992; 326: 1115-22.
• 12. Newcom SR, Tagra KK, Kadin ME. Neutralizing antibodies against transforming growth factor beta potentiate the proliferation of Ki-1 positive lymphoma cells. Further evidence for negative autocrine regulation by transforming growth factor beta. Am J Pathol 1992; 140: 709-18.
• 13. Knaus PI, Lindemann D, DeCoteau JF et al. A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T cell lymphoma. Mol Cell Biol 1996; 16: 3480-9.
• 14. DeCoteau JF, Butmarc JR, Kinney MC et al. The t(2;5) chromosomal translocation is not a common feature of primary cutaneous CD30+ lymphoproliferative disorders: Comparison with anaplastic large cell lymphoma of nodal origin. Blood 1996; 87: 3437-41.
• 15. Tian SG, Longo DL, Funakoshi S et al. In vivo anti-tumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large cell lymphoma. Cancer Res 1995; 55: 5335-41.
• 16. Gruss HJ, Dower SK. Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood 1995; 85: 3378-404.
• 17. Duckett CS, Gedrich RW, Gilfian MC et al. Induction of nuclear factor kB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol 1997; 17: 1535-42.
• 18. Ansieau S, Scheffrahn I, Mosialos G et al. Tumor necrosis factor receptor-associated factors TRAF1, TRAF2 and TRAF3 interact in vivo with HD, Dermel G et al. Tumor necrosis factor receptor-associated factor 1 is overexpressed in ReedSternberg cells of Hodgkin’s disease and EpsteinBarr virus transformed lymphoid cells. Blood 1999; 93: 617-23.
• 20. Bargou RC, Emmerich F, Krappman D et al. Constitutive nuclear factor kB-RelA activation is required for proliferation and survival of Hodgkin’s disease tumor cells. J Clin Invest 1997; 100: 2961-9.
• 21. Filmus J, Kerbel RS. Development of resistance mechanisms to growth inhibitory effects of transforming growth factor-beta during tumor progression. Curr Opin Oncol 1993; 5: 123-9.
• 22. Kadin ME, Cavaille-Coll MW, Gertz et al. Loss of receptors for transforming growth factor beta in human T cell malignancies. Proc Natl Acad Sci USA 1994; 91: 6002-6.
• 23. Schiemann W, Pfeifer WM, Levi E et al. A deletion in the gene for transforming growth factor B type I receptor abolishes growth regulation by TGF-b in a cutaneous T-cell lymphoma. Blood 1999; 94: 2854-61.