Experimental Investigation

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

  • Edi LEVI
  • Walther M. PFEIFER
  • Marshall E. KADIN

Received Date: 25.04.2000 Accepted Date: 09.06.2000 Meandros Med Dent J 2000;1(2):33-37

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