Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole.
The vulnerability of tumour cells to complement-mediated immune attack is regulated by membrane associated molecules. Recently, we have shown that the expression of the membrane attack complex inhibitor CD59 is enhanced on colonic adenocarcinoma cells compared to normal colonic epithelial cells. CD59 was shown, in the same study, to protect the tumour cells from complement-mediated lysis. Levamisole (LMS), used in conjunction with 5-fluorouracil as adjuvant therapy, reduces the incidence of colon cancer relapse following surgical resection. This led to our investigation of the effect of LMS on CD59 expression and function on the human colorectal cell lines HT29 and Caco-2. When cultured in the presence of 10 microM LMS, the cells reduced their expression of CD59 in a time-dependent manner. LMS treated HT29 cells were more sensitive to lysis by complement than control cells, and the reduction in CD59 expression was shown to be partly responsible for this. A reduction in CD59 expression will augment complement-mediated immune surveillance and may contribute to LMSs anti-tumour activity in vivo.
D000230:Adenocarcinoma / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018957:CD59 Antigens / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology*; D003167:Complement Activation; D015536:Down-Regulation; D006801:Humans; D007978:Levamisole / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D018957:CD59 Antigens; D007978:Levamisole