Triple-negative breast cancer (TNBC) is highly aggressive, difficult to treat and commonly develops visceral
metastasis, including lung
metastasis. We observed that High mobility group box 1
protein (
HMGB1) was highly expressed in human TNBC and positively correlated with
cancer metastasis. The hypoxic
tumor environment is known to regulate
HMGB1 secretion, but an understanding of the underlying mechanism by which
tumor-derived
HMGB1 regulates interstitial components and promotes
breast cancer lung
metastasis has remained elusive. The results of the present study showed that the number of CD62Ldim neutrophils, which have a strong ability to produce neutrophil extracellular traps (NETs), increased significantly in both peripheral blood and lung tissues in a mouse TNBC model and were regulated by
tumor-derived
HMGB1 through the TLR2 pathway. Furthermore, serum
HMGB1 levels were positively correlated with CD62Ldim neutrophils in 86
breast cancer patients. We demonstrated that CD62Ldim neutrophils accelerated lung
metastasis and that interventions targeting the "
HMGB1-CD62Ldim neutrophil-NETs" axis could inhibit lung
metastasis. Our results suggest that the combination of
HMGB1 and CD62Ldim neutrophils is a potential marker for
breast cancer lung
metastasis and is novel target for future prevention and
therapy.