Verotoxin (VT) is involved in the etiology of both hemorrhagic colitis and the hemolytic uremic syndrome which are microvasculopathies of the colon and pediatric renal glomerulus respectively. Thus, VT can be considered a vasotoxin. Cell sensitivity in vitro varies according to the receptor glycolipid (globotriaosyl ceramide-Gb3) expression and also to intracellular trafficking of the receptor/toxin complex, such that in highly sensitive cells, the toxin is targeted to the endoplasmic reticulum and nuclear envelope. Such cells include tumor cells which have become drug resistant. Thus Gb3 is upregulated in certain tumors and when such tumor cells become drug resistant, their sensitivity to verotoxin increases. This may be due to a direct role of the MDR1 drug efflux pump in glycolipid biosynthesis. In addition to the tumor tissue, the toxin receptor may also be expressed in the tumor neovasculature suggesting that activated endothelial cells may be verotoxin sensitive. Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed.
Research Article|October 01 1999
Verotoxin/Globotriaosyl Ceramide Recognition: Angiopathy, Angiogenesis and Antineoplasia
C. A. Lingwood
C. A. Lingwood
1Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M4G 1X8
2Department of Biochemistry and Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada
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Biosci Rep (1999) 19 (5): 345-354.
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C. A. Lingwood; Verotoxin/Globotriaosyl Ceramide Recognition: Angiopathy, Angiogenesis and Antineoplasia. Biosci Rep 1 October 1999; 19 (5): 345–354. doi: https://doi.org/10.1023/A:1020299819637
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