TY - JOUR
T1 - Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis
AU - Leng, Xiaohong
AU - Ding, Tian
AU - Lin, Hui
AU - Wang, Yan
AU - Hu, Limei
AU - Hu, Jianhua
AU - Feig, Barry
AU - Zhang, Wei
AU - Pusztai, Lajos
AU - Symmans, W. Fraser
AU - Wu, Yun
AU - Arlinghaus, Ralph B.
PY - 2009/11/15
Y1 - 2009/11/15
N2 - 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-κB 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.
AB - 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-κB 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.
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U2 - 10.1158/0008-5472.CAN-09-1934
DO - 10.1158/0008-5472.CAN-09-1934
M3 - Article
C2 - 19887608
AN - SCOPUS:72249085763
SN - 0008-5472
VL - 69
SP - 8579
EP - 8584
JO - Cancer Research
JF - Cancer Research
IS - 22
ER -