Tesis doctoral de Leticia Corrales Pecino
Given the numerous genetic and epigenetic changes associated with carcinogenesis, tumor cells express antigens that stimulate immune responses such as the complement pathway. However, complement activation may be regulated by malignant cells, avoiding damaging effects. In this study we assessed the capacity of lung cancer cells to regulate complement activation and characterized the biological consequences of this activation. We first measured complement deposition and formation of the membrane attack complex in non-small cell lung cancer cell lines and normal human lung epithelial cells. Lung cancer cell lines spontaneously activated the alternative complement pathway, as measured by c3 deposition. This activation was significantly higher than that in normal human lung epithelial cells. However, at the level of c6 deposition and cell lysis, no significant differences between tumor and normal epithelial cells were observed, suggesting that cancer cells develop inhibitory mechanisms to control complement activation. According to this observation, lung cancer cells treated with an activating polyclonal antibody were significantly more resistant to the activation of the classical complement pathway than normal cells. These results are in agreement with in vivo and in vitro studies that show the development of inhibitory mechanisms by malignant cells to resist complement attack, and with clinical data that demonstrate complement activation in cancer patients. Interestingly, we also observed that 3ll syngeneic tumors grew slower in c3 ko c57bl6 mice than in their normal counterparts. A similar effect was observed when normal mice were treated with an inhibitor of the complement c5a receptor (c5ar). C5a is the most potent anaphylatoxin generated during complement activation. In in vitro studies, c5a stimulated the migration of human umbilical vein endothelial cells and tumor cells, and reduced the adhesion of tumor cells to different extracellular matrix proteins. In conclusion, our study indicates that lung cancer cells are subjected to a harmless, spontaneous and constant complement activation which may in turn promote angiogenesis and tumor progression.
Datos académicos de la tesis doctoral «Complement activation in non-small cell lung cancer and its effects on tumor progression«
- Título de la tesis: Complement activation in non-small cell lung cancer and its effects on tumor progression
- Autor: Leticia Corrales Pecino
- Universidad: Navarra
- Fecha de lectura de la tesis: 18/03/2011
Dirección y tribunal
- Director de la tesis
- Rubén Pio Osés
- Tribunal
- Presidente del tribunal: Santiago Rodriguez de cordoba
- marcin Okroj (vocal)
- Juan José Lasarte sagastibelza (vocal)
- alfredo Martínez ramírez (vocal)