Tumors exploit CXCR4^hiCD62L^lo aged neutrophils to facilitate metastatic spread.

ABSTRACT: Granulocytes are key players in cancer metastasis. While tumor-induced de novo expansion of immunosuppressive myeloid-derived suppressor cells (MDSCs) is well-described, the fate and contribution of terminally differentiated mature neutrophils to the metastatic process remain poorly understood. Here, we show that in experimental metastatic cancer models, CXCR4^hiCD62L^lo aged neutrophils accumulate via disruption of neutrophil circadian homeostasis and direct stimulation of neutrophil aging mediated by angiotensin II. Compared to CXCR4^loCD62L^hi naive neutrophils, aged neutrophils more robustly promote tumor migration and support metastasis through the increased release of several metastasis-promoting factors, including neutrophil extracellul

SUBMITTER: Peng Z 

PROVIDER: S-EPMC7833766 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature