Lipocalin 2 Linked to Breast Cancer Metastasis

Others include their binding to specific cell-surface receptors and their ability to form macromolecular complexes.

Based on earlier studies that showed that lipocalin 2 could be found in the tissues and urine of women with aggressive forms of breast cancer, investigators from Harvard University (Cambridge, MA, USA) undertook a series of experiments to determine how this protein functioned at the molecular level.

The scientists reported in the February 23, 2009, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS) that lipocalin 2 was overexpressed in human breast cancer cells where it upregulated mesenchymal markers, including vimentin and fibronectin, downregulated the epithelial marker E-cadherin, and significantly increased cell motility and invasiveness. These changes in marker expression and cell motility are hallmarks of an epithelial to mesenchymal transition (EMT), which is a characteristic of tumors that are about to progress and metastasize.

Lipocalin 2-expressing breast tumors displayed a poorly differentiated phenotype and showed increased local tumor invasion and lymph node metastasis. In contrast, silencing of lipocalin 2 in aggressive breast cancer cells inhibited cell migration and the transition to the mesenchymal phenotype.

"Our study identifies a novel, additional player in the complex development of invasive breast cancer,” said senior author Dr. Marsha A. Moses, professor of vascular biology at Harvard University. "It suggests that this protein may represent a prognostic and/or therapeutic target for this devastating disease.”

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