Malignant cells are often resistant to complement activation through the enhanced expression of
complement inhibitors. In this work, we examined the protective role of
factor H, CD46, CD55, and CD59 in two
non-small cell lung cancer cell lines, H1264 and A549, upon activation of the classical pathway of
complement.
Complement was activated with polyclonal Abs raised against each cell line. After
blocking factor H activity with a neutralizing Ab, C3 deposition and C5a release were more efficient. Besides, a combined inhibition of
factor H and CD59 significantly increased
complement-mediated lysis. CD46 and CD55 did not show any effect in the control of complement activation.
Factor H expression was knockdown on A549 cells using
small interfering RNA. In vivo growth of
factor H-deficient cells in athymic mice was significantly reduced. C3 immunocytochemistry on explanted xenografts showed an enhanced activation of
complement in these cells. Besides, when mice were depleted of
complement with
cobra venom factor, growth was recovered, providing further evidence that
complement was important in the reduction of in vivo growth. In conclusion, we show that expression of the
complement inhibitor factor H by
lung cancer cells can prevent complement activation and improve
tumor development in vivo. This may have important consequences in the efficiency of
complement-mediated
immunotherapies.