Lipids isolated from bone induce the migration of human breast cancer cells

• Published in: Journal of lipid research 2006-04, Vol.47 (4), p.724-733
• Main Authors: Silva, Jeane, Dasgupta, Somsankar, Wang, Guanghu, Krishnamurthy, Kannan, Ritter, Edmond, Bieberich, Erhard
• Format: Article
• Language: English
• Subjects: Actins - metabolism; bile acids; Bone and Bones - chemistry; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - physiology; Cell Survival; Culture Media, Conditioned; deoxycholate; Deoxycholic Acid - chemistry; Deoxycholic Acid - metabolism; DNA-Binding Proteins - metabolism; farnesoid X receptor; Female; Humans; Lipids - isolation & purification; Receptors, Cytoplasmic and Nuclear - metabolism; Transcription Factors - metabolism; urokinase-type plasminogen activator; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M500473-JLR200

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 the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell self-propel its migration and metastasis to the bone.