Breast cancer induces CD62L⁺ Kupffer cells via DMBT1 to promote neutrophil extracellular trap formation and liver metastasis.

ABSTRACT: The liver is a major target organ for breast cancer metastasis, while the regulatory mechanism of liver colonization by breast cancer remains largely unclear. Neutrophils are known to play important roles in metastatic colonization of cancer cells by the formation of neutrophil extracellular traps (NETs). Here we show the role and mechanism of a subpopulation of Kupffer cells (KCs), the liver resident macrophages, in mediating tumoral induction of NETs and liver metastasis. NETs are activated more abundantly in liver metastases of breast cancer, as compared to metastases to other organs and primary tumors. Liver-tropic tumor cells induce CD62L-expressing KCs by a secretory protein DMBT1, and CD62L⁺ KCs activate neutrophils for NETosis via the chemokine CCL8. Inhibition of CCL8 o

SUBMITTER: Tian P 

PROVIDER: S-EPMC12343785 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature