Untangling the Connection Between Stress and Metastatic Cancer

ASPIRE Award (2019-2020)

Mikala Egeblad, PhD, Cold Spring Harbor Laboratory

Mikala Egeblad, PhD

Despite great strides in cancer treatment, once cancer has metastasized, it is often impossible to cure. Metastases can form long after the primary tumor has been removed or otherwise treated, suggesting a delay between the time when tumor cells initially spread to other tissues and when they overcome the body’s immune defenses and proliferate. Clinical observations suggest that stress can drive the process of metastasis. For example, cancer patients who experience chronic stress develop metastatic cancer sooner than those who do not.  The mechanism by which this happens, however, is not well understood. The Egeblad lab has recently demonstrated that neutrophils, a type of immune cell, play an important role in metastasis. Neutrophils target bacteria and other microorganisms by trapping them within web-like structures called NETs (neutrophil extracellular traps) composed of DNA and enzymes. Cancer cells have the remarkable ability to hijack nearby neutrophils, forcing them to eject NETs, which may help prepare the local microenvironment for metastatic colonization. In this project, researchers will explore whether increased NET formation contributes to the increased propensity of cancer to metastasize under conditions of chronic stress. They will also look at how NETs induce changes in the immune microenvironment surrounding the cancer cells that allow the cells to proliferate. By providing insight into the biological pathways by which stress can lead to the growth and resilience of tumor cells that have escaped the primary tumor site, this research will provide critical information needed to develop new drugs to prevent or treat metastatic cancer.

Published research

He XY, Gao Y, Ng D, Michalopoulou E, George S, Adrover JM, Sun L, Albrengues J, Daßler-Plenker J, Han X, Wan L, Wu XS, Shui LS, Huang YH, Liu B, Su C, Spector DL, Vakoc CR, Van Aelst L, Egeblad M. Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment. Cancer Cell. 2024.