sq-23377 and globotriaosylceramide

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.

Topics: Antibodies, Monoclonal; B-Lymphocytes; bcl-X Protein; Burkitt Lymphoma; CD40 Ligand; Cell Death; Cell Line; DNA; Escherichia coli; Humans; Ionomycin; Protein Subunits; Proto-Oncogene Proteins c-bcl-2; Receptors, Cell Surface; Shiga Toxin 1; Signal Transduction; Trihexosylceramides