Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth

Munir H, Jones JO, Janowitz T, Hoffmann M, Euler M, Martins CP, Welsh SJ, Shields JD (2021)


Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 12

Article Number: 683

Journal Issue: 1

DOI: 10.1038/s41467-021-20982-2

Abstract

Tumors consist of cancer cells and a network of non-cancerous stroma. Cancer-associated fibroblasts (CAF) are known to support tumorigenesis, and are emerging as immune modulators. Neutrophils release histone-bound nuclear DNA and cytotoxic granules as extracellular traps (NET). Here we show that CAFs induce NET formation within the tumor and systemically in the blood and bone marrow. These tumor-induced NETs (t-NETs) are driven by a ROS-mediated pathway dependent on CAF-derived Amyloid β, a peptide implicated in both neurodegenerative and inflammatory disorders. Inhibition of NETosis in murine tumors skews neutrophils to an anti-tumor phenotype, preventing tumor growth; reciprocally, t-NETs enhance CAF activation. Mirroring observations in mice, CAFs are detected juxtaposed to NETs in human melanoma and pancreatic adenocarcinoma, and show elevated amyloid and β-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid β as the protagonist and potential therapeutic target.

Authors with CRIS profile

Involved external institutions

How to cite

APA:

Munir, H., Jones, J.O., Janowitz, T., Hoffmann, M., Euler, M., Martins, C.P.,... Shields, J.D. (2021). Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth. Nature Communications, 12(1). https://dx.doi.org/10.1038/s41467-021-20982-2

MLA:

Munir, Hafsa, et al. "Stromal-driven and Amyloid β-dependent induction of neutrophil extracellular traps modulates tumor growth." Nature Communications 12.1 (2021).

BibTeX: Download