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Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Leng, Xiaohong Ding, Tian Ming Lin, Hui Can Wang, Yan Hu, Limei Hu, Jianhua Feig, Barry Zhang, Wei Pusztai, Lajos Symmans, W. Fraser Wu, Yun Arlinghaus, Ralph B. |
| Copyright Year | 2009 |
| Abstract | 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. |
| Starting Page | 1061 |
| Ending Page | 1076 |
| Page Count | 16 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/69/22/8579.full.pdf |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/early/2009/11/03/0008-5472.CAN-09-1934.full.pdf |
| PubMed reference number | 19887608v1 |
| Alternate Webpage(s) | https://doi.org/10.1158/0008-5472.CAN-09-1934 |
| DOI | 10.1158/0008-5472.can-09-1934 |
| Journal | Cancer research |
| Volume Number | 69 |
| Issue Number | 22 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Animal Mammary Neoplasms Carcinogenesis Cell secretion ERBB2 protein, human LCN2 protein, human Lipocalin-2 Measurement Lipocalins Matrix Metalloproteinase 9 Mouse mammary tumor virus NF-kappa B Proto-Oncogene Proteins c-akt lung metastases trastuzumab |
| Content Type | Text |
| Resource Type | Article |
