L. Bjorge et al., RESISTANCE OF OVARIAN TERATOCARCINOMA CELL SPHEROIDS TO COMPLEMENT-MEDIATED LYSIS, British Journal of Cancer, 75(9), 1997, pp. 1247-1255
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.