Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

Nat Commun. 2020 Jun 24;11(1):3193. doi: 10.1038/s41467-020-16890-6.

Abstract

Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology*
  • Cell Transformation, Neoplastic / drug effects
  • Chronic Disease
  • Chronobiology Disorders / complications*
  • Chronobiology Disorders / genetics
  • Chronobiology Disorders / immunology
  • Cytokines / genetics
  • Female
  • Gene Expression Regulation
  • Immunosuppression
  • Light Signal Transduction / genetics
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis / prevention & control
  • Receptors, Interleukin-8B / antagonists & inhibitors
  • Receptors, Interleukin-8B / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Cxcr2 protein, mouse
  • Cytokines
  • Receptors, Interleukin-8B