Lipocalin 2 promotes lung metastasis of murine breast cancer cells.
BACKGROUND
Lipocalin 2, an iron binding protein, is abnormally expressed in some malignant human cancers and may play an important role in tumor metastasis. However, the roles of lipocalin 2 in breast cancer formation and metastasis have not been clearly shown. This study aimed to investigate the roles of lipocalin 2 in breast tumor metastasis.


METHODS
Lipocalin 2 was overexpressed in the metastatic 4T1 murine mammary cancer cells. The effects of lipocalin 2 overexpression on the malignancy of breast cancer cells were examined using cell proliferation assay, migration assay, invasion assay, and soft agar assay in vitro. Tumor formation and metastasis abilities were examined using a well established mouse mammary tumor model in vivo.


RESULTS
Lipocalin 2 overexpression significantly enhanced the migration and invasion abilities of 4T1 cells in vitro, and lung metastasis in vivo. But overexpression of lipocalin 2 in 4T1 cells didn't affect cell proliferation and anchorage-independent growth in vitro, and primary tumor weight in vivo. Further studies demonstrated that the inhibition of the PI3K/Akt pathway could be a causative mechanism for the promotion of breast cancer migration/invasion induced by lipocalin 2 overexpression.


CONCLUSIONS
These results clarified that lipocalin 2 could promote lung metastasis of 4T1 cells through the inhibition of the PI3K/Akt pathway, suggesting that lipocalin 2 was a potential target for therapy of breast cancer.
Shi
Han
H
Department of Molecular Biology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, PR China. zhtshh@163.com
Gu
Yuchao
Y
Yang
Jing
J
Xu
Liang
L
Mi
Wenyi
W
Yu
Wengong
W
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D015674:Mammary Neoplasms, Animal; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse