Protection of human breast cancer cells from complement-mediated lysis by expression of heterologous CD59

CD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) a re widely expressed cell surface glycoproteins that protect host cells from the effects of homologous complement attack. Complement inhibitory activit y of these proteins is species-selective. We show that the human breast can cer cell line MCF7 is relatively resistant to lysis by human complement, bu t is effectively lysed by rat or mouse complement. CD59, DAF and MCP were a ll shown to be expressed by MCF7. The species-selective nature of CD59 acti vity was used to demonstrate directly the effectiveness of CD59 at protecti ng cancer cells from complement-mediated lysis. cDNAs encoding rat and mous e CD59 were separately transfected into MCF7 cells, and cell populations ex pressing high levels of the rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were highly effective at protecting transfect ed MCF7 cells from lysis by rat and mouse complement, respectively. Data fu rther reveal that rat CD59 is not effective against mouse complement, where as mouse CD59 is effective against both mouse and rat complement. These stu dies establish a model system for relevant in vivo studies aimed at determi ning the effect of complement regulation on tumourigenesis, and show that f or effective immunotherapy using complement-activating anti-tumour antibodi es, the neutralization of CD59 and/or other complement inhibitory molecules will probably be required.