CONICET | Buscador de Institutos y Recursos Humanos

Circadian rhythm disruption as a modern life consequence (shiftwork, jetlag, etc.) may lead to metabolic disorders or higher cancer risk. Cancer cells display aberrant proliferation with a very active metabolism to facilitate tumor growth and metastasis. However, little is known about the circadian clock function on tumor growth regulation. Here we investigate the day/night differences in the growth of peripheral tumors of sciatic nerve after the inoculation of A530 glioma cells isolated from NPcis (Trp53+/-; Nf1 +/-) heterozygous mice, a human neurofibromatosis type I model. In A530 cultures, mRNA of clock and clock-controlled genes, levels of ROS and susceptibility to Bortezomib chemotherapy exhibited temporal fluctuations. When A530 cells were injected into the sciatic nerve of C57BL/6 mice during the morning or the night of a 12:12 h L/D cycle, tumors growing on animals injected during the night showed a higher rate of growth as compared with those injected at day. Day/night differences were also found after subcutaneous inoculation of melanoma B16 cells in mice at day or night with higher values observed in males of night group. Lastly, when we examined the role of the molecular clock activator Bmal1 in tumor growth, a higher rate of tumor growth was found when Bmal1 expression was diminished by CRISPR/Cas9 in A530 cells compared with controls. Our observations strongly suggest that the tumor growth is subject to temporal control and mainly dependent on the host state.