CD40 ligand, Bcl-2, and Bcl-xL spare group I Burkitt lymphoma cells from CD77-directed killing via Verotoxin-1 B chain but fail to protect against the holotoxin (Journal article)

Gordon, J./ Challa, A./ Levens, J. M./ Gregory, C. D./ Williams, J. M./ Armitage, R. J./ Cook, J. P./ Roberts, L. M./ Lord, J. M.

Owing to its lineage and differentiation stage-restricted expression, CD77 has been mooted as a therapeutic target in Burkitt lymphoma (BL). The recognition that the globotriaosyl moiety of this neutral glycosphingolipid is a receptor for Escherichia coli-derived Verotoxin-1 (Shiga-Like Toxin-1) offers a potential delivery system for the attack. Here we show that CD77-expressing Group I BL cells which are normally susceptible to activation-induced death on binding Verotoxin-1 B chain are protected in the presence of CD40 ligand. Ectopic expression of either bcl-2 or bcl-xL also afforded resistance to the actions of the B chain. In total contrast, neither of the survival genes nor a CD40 signal - even when acting in concert - protected against killing mediated by the holotoxin. These findings indicate that while therapeutic modalities for CD77-expressing B cell tumors (which include follicular lymphoma) based on the use of Verotoxin-1 B chain might be compromised by the activation of endogenous or exogenous survival pathways, those exploiting the holotoxin should be left unscathed.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Antibodies, Monoclonal/pharmacology,B-Lymphocytes/drug effects/*metabolism,Burkitt Lymphoma/drug therapy/*metabolism/pathology,CD40 Ligand/*metabolism/pharmacology,Cell Death,Cell Line,DNA/metabolism,Escherichia coli/metabolism,Humans,Ionomycin/pharmacology,Protein Subunits,Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism,Receptors, Cell Surface/*metabolism,Shiga Toxin 1/metabolism/*pharmacology/therapeutic use,Signal Transduction,Trihexosylceramides/*metabolism,bcl-X Protein
ISSN: 1350-9047
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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