Lipids isolated from bone induce the migration of human breast cancer cells.
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.
Silva
Jeane
J
Institute of Molecular Medicine and Genetics,School of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
Dasgupta
Somsankar
S
Wang
Guanghu
G
Krishnamurthy
Kannan
K
Ritter
Edmond
E
Bieberich
Erhard
E
D000199:Actins / Q000378:metabolism; D001842:Bone and Bones / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins / Q000378:metabolism; D003840:Deoxycholic Acid / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000302:isolation & purification*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
D000199:Actins; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D003840:Deoxycholic Acid; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator; D000099150:Receptor, Farnesoid X-Activated