Metastasis-promoting protein identified; could provide a prognostic test or target for breast cancer

Researchers led by Marsha A. Moses, PhD, and Jiang Yang, PhD, of the Vascular Biology Program at Children's, induced human breast cancer cells to make large amounts of lipocalin 2, and showed that cell motility and invasiveness increased significantly. They then took cells from aggressive breast cancers and silenced lipocalin 2, and found that cell migration was significantly inhibited. When they transplanted human breast cancer cells into animals, those from tumors making lipocalin 2 were more locally invasive and more likely to metastasize to lymph nodes.

Further laboratory studies indicated that lipocalin 2 decreases the levels of estrogen receptor alpha, thereby reducing the cells' response to the hormone estrogen, which is associated with poor prognosis of breast cancer. Inhibiting the production of estrogen receptor alpha is also the mechanism that triggers the EMT pathway, the researchers show.

Finally, tissue samples, and even urine samples, from women with invasive breast cancer consistently showed elevated lipocalin 2 levels, suggesting that testing for lipocalin 2 may be a way of detecting cancer progression and the need for more aggressive treatment.

"Our study identifies a novel, additional player in the complex development of invasive breast cancer," says Moses, the Vascular Biology Program's interim director. "It suggests that this protein may represent a prognostic and/or therapeutic target for this devastating disease."

Source: Children's Hospital Boston