IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neuroimmune communication between the circadian clock and tumor development in mice
Autor/es:
ROMÁN, FERNANDA; RICHARD, SILVINA MARIEL; AIELLO, IGNACIO; PALADINO, NATALIA; CERLIANI, MARÍA BELÉN; GOLOMBEK, DIEGO; MUL FEDELE, MALENA; CHIESA, JUAN JOSÉ
Lugar:
Chicago
Reunión:
Congreso; Experimental Biology 2017; 2017
Institución organizadora:
AAA, APS, ASBMB, ASIP, ASN, ASPET
Resumen:
Daily environmental changes on Earth have imposed a selective pressure for life driving the development of circadian clock mechanisms that generate rhythms in physiological and behavioral variables, and are capable of entraining to external cues. In mammals, the clock resides in the hypothalamic suprachiasmatic nuclei (SCN), and the principal signal that adjusts its activity is the light-dark (LD) cycle. Bidirectional interactions between the immune and the circadian systems have been under intensive study in recent years. Particularly, it has become very important the role of the circadian clock in tumor progression. According to the World Health Organization, work schedules that imply a desynchronization between the circadian system and the environmental and social factors, such as shift work, represent a risk factor for the development of cancer. Moreover, it?s known that tumor growth can be regulated by genes that are part of the molecular circadian clock.Our purpose is to determine the effect of circadian desynchronization induced by chronic jet-lag (CJL) in tumor development, focusing in the role of the immune system. We injected subcutaneously B16 cells (murine melanoma) in C57bl/6 mice housed under CJL (6 h advances every 2 days) or normal light (LD 12:12) conditions. Our results show that the tumor growth rate was significantly higher, while latency was lower under CJL condition. However, early tumor angiogenesis was not affected. In addition, tumor and liver expression of clock genes Per1?2 were decreased under CJL condition, but levels of the clock gene Bmal1 were similar under both conditions. We have also studied the proinflammatory response in the tumors of these animals at two different time points, and we found that the levels of cytokines TNF-α, IL-6 and IL?1β were induced during the day in animals living in normal light conditions, while the expression was similar at both time points in animals subjected to circadian desynchronization. Additionally, the spleen percentage of mature antigen-presenting cells was decreased under CJL schedule.For the other hand, animals carrying tumors showed a decrease in the percentage of nocturnal activity and in the strength of their locotomor activity rhythms in LD conditions. We have also analyzed the mRNA levels of the chemokine Ccl2/MCP-1 (Monocyte Chemotactic Protein-1) and TNF-α in the SCN of animals subjected to normal light conditions. The first one seems to increase in the SCN of animals with the tumor, while the other one was undetectable.In conclusion, here we show that the bidirectional interaction between the immune and circadian systems can be mediated by cytokines/chemokines in a murine model tumor development. We have also confirmed that circadian desynchronization can affect the development of a tumor and that the inflammatory molecules present in the tumor are over circadian control.