Interfering Breast Cancer Metastases by Blocking NGAL Function PRINCIPAL INVESTIGATOR:

Lipocalin 2 (LCN2, also known as NGAL) is a secreted glycoprotein and its elevated expression has been observed in breast cancers. However, the importance of LCN2 in breast tumorigenesis is unclear. Here, we employed a spontaneous mammary tumor mouse model showing that MMTV-ErbB2(V664E) mice lacking of mLCN2 had significantly delayed mammary tumor formation and metastasis with reduced MMP-9 activity in the blood. LCN2 expression is upregulated by HER2/PI-3 kinase/AKT/NF-κB pathway. Decreasing LCN2 expression significantly reduced the invasion and migration ability of HER2 breast cancer cells. Furthermore, injecting an anti-mLCN2 antibody into mice bearing established murine breast tumors resulted in significant blockage of lung metastasis. Our findings indicate that LCN2 is a critical factor in enhancing breast tumor formation and progression, possibly in part by stabilizing MMP-9. Our results suggest that inhibition of LCN2 function by an inhibitory