Expresión del factor h en cáncer de pulmón y su papel protector frente a la activacióhn del sistema del complemento

Resumen

The complement system is a part of the innate immunity that plays an important role against tumors. However, malignant cells are usually resistant to complement through the enhanced expression of complement control proteins. In this study we show that most non small cell "lung cáncer (nsclc) cells produce and bind factor H, an inhibitor of complement activation, as a mechanism to escape the activation of both the alternative and the classical pathways of complement. When factor H activity was blocked by a neutral izing antibody, deposition of C3 fragments and C5a reléase from normal human serum was more efficient, and the susceptibility to complement-mediated lysis was increased. Finally, in order to evaluate the in vivo role of factor H, we knocked down factor H expression on A549 cells using siRNA silencing of the gene. Growth of xenograft tumors in athymic mice after the stimulation of both the alternative and the classical pathway of the complement were significantly reduced when the expression of factor H was blocked. In summary, we have shown that lung cancer cells are able to prevent significant complement activation upon their cell membrane improving tumor development in vivo. We demonstrate that lack of activation can be prevented by factor H inhibition. Our results suggest that complement-mediated immunotherapy based on modulation of complement activation is an attractive strategy for lung cancer treatment