Circadian‐rhythm‐regulating hormones: Key factors to regulate breast cancer metastasis via circulating tumor cells

Recently, a study in Nature, Diamantopoulou et al. presented breast cancer metastasizes faster during sleep in both mouse models and breast cancer patients.The circulating tumor cells (CTCs), as pioneers of the breast metastasis, were regulated by circadian-rhythm-regulating hormones in terms of both the level and activity in the blood (Figure 1). 1 Among the many cancers, breast cancer is prone to metastasis.While, once metastasis occurs, treatment can become very tricky.Metastasis of breast cancer is mainly through the hematogenous dissemination of CTCs. 2 However, current research has not focused much on when tumors shed cells and metastasize.By collecting and analyzing blood samples from 30 female breast cancer patients (nine with stage IV metastatic breast cancer and 21 with early breast cancer and no metastasis) at different points in the day, the authors first found the levels of CTCs in blood samples collected during nighttime sleep (4 a.m.) is significantly higher than that collected in daytime activity (10 a.m.).To further verify the generality of the events, the authors constructed four different mouse models of breast cancer (i.e., an immunocompetent syngeneic breast cancer model, xenografts obtained from human breast CTCs, and two xenografts with established mouse breast cancer cells or human breast cancer cells, respectively).The microfluidic