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CD30-induced mechanisms in lymphoma
CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is consistently expressed in tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Disclosure of CD30 signaling is conducted on the cellular, mRNA, microRNA and protein level, linked to the vision of targeting CD30 in therapy successfully.
CD30-stimulation activates NFκB whereby apoptosis is inhibited. However, CD30 stimulation induces massive apoptosis in case of canonical NFκB inhibition. This dualism of CD30 signaling is only marginally understood and currently under investigation. To this end, expression and CD30-mediated regulation of components of the TNFR-family-signaling-cascades are analyzed in vitro and in specimens of CD30-positive neoplasia. We recently identified RIP1 to be a critical component of CD30-induced cell death in ALCL cell lines.
Hirsch B, Von der Wall E, Hummel M, Dürkop H. RIP1 expression is necessary for CD30-mediated cell death induction in Anaplastic Large Cell Lymphoma Cells. Lab Invest, 2013 Apr 1, PMID: 23545938
Hirsch B, Grünbaum M, Wagner F, Bi Y, Lucka L, Du MQ, Stein H, Dürkop H. A novel A20 (TNFAIP3) antibody (Ber-A20) can be used to detect unmutated A20 by immunohistology. Histopathology, 2012 May; 60(6B):E19-27, PMID: 22393903
Hirsch B, Braun FK, Al-Yacoub N, Assaf C, Kadin ME, Sterry W, Eberle J, Dürkop H. cFLIP diminishes CD95-induced apoptosis of CD30-stimulated cutaneous anaplastic large T cell lymphoma (cALCL) cells. Pathologe. 2010 Oct; 31 Suppl 2:193-8. PMID: 20812013
Hirsch B, Brauer J, Fischdick M, Loddenkemper C, Bulfone-Paus S, Stein H, Dürkop H. Anti-CD30 human IL-2 fusion proteins display strong and specific cytotoxicity in vivo. Curr Drug Targets. 2009 Feb; 10(2):110-7. PMID: 19199906
Hirsch B, Hummel M, Bentink S, Fouladi F, Spang R, Zollinger R, Stein H, Dürkop H. CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells. Am J Pathol. 2008 Feb; 172(2):510-20. PMID: 18187570
Suzuki O, Hirsch B, Abe M, Dürkop. Galectin-1-mediated cell death is increased by CD30-induced signaling in anaplastic large cell lymphoma cells but not in Hodgkin lymphoma cells. H, Stein H.Lab Invest. 2011 Oct 10. doi: 10.1038/labinvest.2011.151. PMID: 21986812
Braun FK, Hirsch B, Al-Yacoub N, Dürkop H, Assaf C, Kadin ME, Sterry W, Eberle J. Resistance of cutaneous anaplastic large-cell lymphoma cells to apoptosis by death ligands is enhanced by CD30-mediated overexpression of c-FLIP. J Invest Dermatol. 2010 Mar; 130(3):826-40. PMID:19890350