Extended Data Fig. 3: Circadian rhythm and melatonin regulate the intravasation of CTCs.

a, Illustration of the experimental design for “b” and “e”. b, Box plots showing the mean number of CTCs isolated from NSG-LM2 (n = 5; single CTCs P = 0.0079, CTC clusters P = 0.0079, CTC-WBC clusters P = 0.0317) and NSG-4T1 (n = 4; P = 0.0286 for all) mice that were kept in standard light cycle conditions (12:12, LD) or being jet-lagged. The blood draw was performed at ZT4. c, Plots showing the mean fold change decrease of CTC counts upon jet lag in NSG-LM2 (n = 5) and NSG-4T1 (n = 4) mice shown in “b”. d, Plots showing the size of primary tumors dissected from NSG-LM2 (n = 5) and NSG-4T1 (n = 4) mice shown in “b”. Data are presented as mean ± s.e.m. e, Box plots showing the distribution of the number of CTCs isolated from NSG-LM2 mice that were being jet-lagged (left) or kept in standard light cycle conditions (right) and were treated with melatonin alone or in combination with its antagonist luzindole. The blood draw was performed at ZT4 or ZT0. (n = 4, except control and melatonin-treated mice in combination with luzindole at ZT4 where n = 5; ZT4 P = 0.0159 except CTC-WBC clusters treated with melatonin in combination with lunzindole where P = 0.0317; ZT0 P = 0.0286 except single CTCs treated with melatonin in combination with lunzindole where P = 0.0091). f, Plots showing the size of primary tumors dissected from mice shown in “e”. Data are presented as mean ± s.e.m. g, Representative bioluminescence images of lungs from NSG-LM2 mice that were kept in standard light cycle conditions (12:12, LD) and were treated with melatonin alone or in combination with luzindole. For panels ‘b’ and “e”, center lines in the box represent the median; box limits represent first and third quartile; extremes of the whisker lines represent the minimum and maximum observed values. * P < 0.05, ** P < 0.01 by two-sided Mann-Whitney test. For all panels, n represents the number of biologically independent mice

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