| First Author | Munir H | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 683 |
| PubMed ID | 33514748 | Mgi Jnum | J:301013 |
| Mgi Id | MGI:6504848 | Doi | 10.1038/s41467-021-20982-2 |
| Citation | Munir H, et al. (2021) Stromal-driven and Amyloid beta-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat Commun 12(1):683 |
| abstractText | 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 beta, 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 beta-Secretase expression which correlates with poor prognosis. In summary, we report that CAFs drive NETosis to support cancer progression, identifying Amyloid beta as the protagonist and potential therapeutic target. |
