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

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

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)724-733
Number of pages10
JournalJournal of Lipid Research
Volume47
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Bile acids
  • Deoxycholate
  • Farnesoid X receptor
  • Urokinase-type plasminogen activator

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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