V-026
Bidirectional interaction between circadian system and metastatic development in mice
Guido Hokama1, Ignacio Aiello2, Ignacio Miguel1, Camila Senna1, Diego Golombek3, Carla Finkielstein2,4, Natalia Paladino1
  1. Laboratorio de Cronobiología, Universidad Nacional de Quilmes, Buenos Aires, Argentina
  2. Integrated Cellular Responses Laboratory, Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, 24016, USA
  3. Laboratorio Interdisciplinario del Tiempo y la Experiencia (LITERA), Universidad de San Andrés, Buenos Aires, Argentina
  4. Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24060, USA
Presenting Author:
Guido Hokama
guidohokama98@gmail.com
Most physiological and behavioral functions exhibit daily rhythms synchronized with the light-dark (LD) cycle. Shift and night work desynchronizes biological rhythms, promoting cancer development. Previously, we reported in a non-metastatic murine melanoma model that chronic jet-lag (CJL, 6-hour advance of the LD cycle every 2 days) increases tumor growth rate and disrupts rhythms in immune parameters. Here, we evaluated a metastatic murine melanoma, which induces lung metastasis, in two circadian desynchronization models: CJL and Per2brdm1 mutant mice. We observed an increased metastatic development in both desynchronized mice. Regarding immune system, we found daily patterns in lung macrophage levels under LD: M1 (anti-tumoral) cells peak at the late night, while M2 (pro-tumoral) peak at the early night. These patterns were disrupted in desynchronized mice. On another hand, the deregulation of clock-related parameters has been observed in cancer patients, therefore we evaluated if metastasis development alters body rhythms. We observed a disruption in temperature rhythms, and a decrease in the strengths of locomotor activity. These findings show a bidirectional interaction between the circadian system and metastatic process: circadian desynchronization promotes metastatic development, maybe partly through immune system modulation, while the circadian system itself gets worse during tumor progression which could initiate a vicious cycle and facilitate tumor growth.