RESISTANCE OF OVARIAN TERATOCARCINOMA CELL SPHEROIDS TO COMPLEMENT-MEDIATED LYSIS

We have shown previously that it is possible to target complement-medi ated killing against cultured ovarian tumour cells in vitro, As malign ant ovarian cells usually grow in solid nodules in vivo, we have in th e present study examined the effectiveness of complement killing again st ovarian teratocarcinoma cells (PA-1) growing in three-dimensional t umour microspheroids (TMSs), Our study shows that PA-1 cells growing i n TMSs are less susceptible to complement-mediated killing than cells growing in monolayer cultures, even after neutralization of protectin (CD59), the main inhibitor of complement lysis, Cells in suspension an d cells growing in TMSs showed a similar expression of membrane co-fac tor protein (MCP, CD46) and CD59, Decay-accelerating factor (DAF, CD55 ) was not detected on the surface of cells in suspension, but appeared focally on the outermost cell layers of the TMSs, Complement-activati ng antibodies bound to all PA-1 cells in suspension but only to the mo st peripherally located cells in TMSs, even though the target antigens were similarly expressed in the two systems. Antibody-induced complem ent activation on PA-1 cells in suspension led to C3 and C5b-9 deposit ion on most cells, while C3 and C5b-9 were only found on the outermost layers of the TMSs. The increased complement resistance of tumour cel ls growing in three-dimensional spheroids is partly because of an insu fficient penetration of antibodies and complement into the TMSs. TMSs are a useful model for the development of more efficient ways to kill malignant cells in micrometastases with monoclonal antibodies and comp lement.