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A more recent version of this article appeared on April 1, 2006

Papers In Press, published online ahead of print January 26, 2006
J. Lipid Res., doi:10.1194/jlr.M500473-JLR200
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Submitted on October 31, 2005
Revised on December 19, 2005
Accepted on January 26, 2006

Lipids isolated from bone induce migration of human breast cancer cells

Jeane Silva, Somsankar Dasgupta, Guanghu Wang, Kannan Krishnamurthy, Edmond Ritter, and Erhard Bieberich

Medical College of Georgia, Augusta

Corresponding Author: ebieberich{at}mail.mcg.edu

Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor (FXR) antagonist Z-guggulsterone prevents migration of these cells and induces apoptosis. DC elevates the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with elevation of uPA (urokinase-type plasminogen activator) and formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced elevation of uPA and binding to the uPA receptor of the same breast cancer cell self-propels its migration and metastasis to the bone.


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