ENHANCED SENSITIVITY OF P-GLYCOPROTEIN-POSITIVE MULTIDRUG-RESISTANT TUMOR-CELLS TO COMPLEMENT-MEDIATED LYSIS

The interaction of KB-V1, a multidrug resistant (MDR) variant of the K B-3-1 human oral carcinoma, with human complement was investigated. KB -V1 cells were found to be more sensitive than KB-3-1 cells to complem ent-mediated lysis. Detailed analysis of the capacity of KB cells to a ctivate human complement demonstrated that both C3b deposition and for mation of the membrane attack complex (MAC) are higher on KB-V1 than o n KB-3-1 cells, Furthermore, the MAC formed on KB-V1 cells, but not on KB-3-1 cells, was found to be resistant to trypsin treatment, i.e. mo re stably inserted into the plasma membrane. Immunofluorescence analys is by flow cytometry showed that KB-V1 cells express less decay-accele rating factor (DAF, CD55) than KB-3-1 cells. Two other complement regu latory proteins. membrana cofactor protein (MCP, CD46) and CD59 are ex pressed to a similar extent on both KB-V1 and KB-3-1 cells. Treatment of KB-V1 cells with neutralizing anti-P-glycoprotein (P-gp) monoclonal antibodies reduced their sensitivity to complement. In addition, KB-V 1 revertants which cease to express P-gp become more resistant to comp lement. These results indicate that multiple factors, such as reduced expression of DAF, enhanced deposition of C3b and increased binding an d stability of the MAC may contribute to the increased complement sens itivity of KB-V1 cells. It is suggested that P-gp is responsible for t he complement-sensitive phenotype of KB-V1 cells.