| First Author | Leng X | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 22 | Pages | 8579-84 |
| PubMed ID | 19887608 | Mgi Jnum | J:154442 |
| Mgi Id | MGI:4368030 | Doi | 10.1158/0008-5472.CAN-09-1934 |
| Citation | Leng X, et al. (2009) Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res 69(22):8579-84 |
| abstractText | 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 mouse LCN2 had significantly delayed mammary tumor formation and metastasis with reduced matrix metalloproteinase-9 activity in the blood. LCN2 expression is upregulated by HER2/phosphoinositide 3-kinase/AKT/NF-kappaB pathway. Decreasing LCN2 expression significantly reduced the invasion and migration ability of HER2(+) breast cancer cells. Furthermore, injecting an anti-mouse LCN2 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 matrix metalloproteinase-9. Our results suggest that inhibition of LCN2 function by an inhibitory monoclonal antibody has potential for breast cancer therapy, particularly by interfering with metastasis in aggressive types of breast cancer. |
