The primary cause of cancer-related deaths today is metastasis, a process by which tumor cells spread to other tissues and form lesions there. Once disseminated, these tumor cells can stay “dormant” for years until they begin to grow, but the factors that trigger this growth aren’t fully understood. Stress-associated glucocorticoids (GCs) appear to be an important factor, especially in breast cancer, where severe life events are associated with a nine-fold increase in risk of relapse. GCs can impact the activity of the immune system, especially immune cells called neutrophils, which play a major role in metastasis through the formation of neutrophil extracellular traps (NETs). GC stress is known to influence neutrophils, and increases breast cancer metastasis in mice in a NET-dependent way.
In this project, Dr. Adrover will study how GC stress affects the ability of neutrophils to form metastasis-promoting NETs and seeks to characterize the mechanisms responsible. Specifically, he will determine whether GC stress affects immune stem cells in the bone marrow and primes neutrophils toward NET formation, and clarify how exactly NETs impact the activity of metastatic tumor cells. Overall, his project aims to establish a new framework for how GC stress promotes cancer relapse, which has the potential to open up new therapeutic opportunities against cancer.
Projects and Grants
Role of Stress-Induced Priming of Neutrophils in Breast Cancer
Cold Spring Harbor Laboratory | Breast Cancer | 2020 | Mikala Egeblad, Ph.D.
Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection
Jose M. Adrover et al | JCI Insight | 2022 | DOI
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