Neuroimmune communication between the circadian clock and tumor development in mice

ROMÁN, FERNANDA; MUL FEDELE, MALENA; CERLIANI, MARÍA BELÉN; RICHARD, SILVINA MARIEL; CHIESA, JUAN JOSÉ; GOLOMBEK, DIEGO; PALADINO, NATALIA

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2015

Sociedad Argentina de Investigación en Neurociencias (SAN)

Circadian disruption related to shift-work and jet-lag has been established as a health hazard in both humans and animal models. The mechanisms by which these conditions lead to such a wide range of deleterious effects are still unclear. It has been shown that circadian disruption increases the incidence of different types of cancer. Our purpose is to determine the effect of chronic jet-lag (CJL) in tumor development, focusing in the role of the immune system. We injected subcutaneously B16 cells in C57bl/6 mice housed under CJL (6 h advances every 2 days) or normal light (LD 12:12) conditions. We compared tumor latency and growth, survival and variations in immune and circadian variables. Our resultsshow that the tumor growth rate was significantly higher, while survival and latency was lower under CJL condition. However, early tumor angiogenesis was not affected. In CJL conditions, tumor levels of pro-inflammatory cytokines Interleukin (IL)-6, IL-1β and Tumor Necrosis Factor (TNF)-α lost their LD expression patterns (which tend to be higher during the day). In addition, tumor expression of clock genes Per1 and 2 were decreased in this group. Moreover, animals under CJL schedule showed an increase in TNF-α and the chemokine CCL2 levels in the hypothalamic suprachiasmatic nucleus at night. In summary, we conclude that the CJL schedules increased the rate of tumor development in mice and circadian modifications in immune variables may be implicated in this association.