Osteoblast-derived oxysterol is a migration-inducing factor for human breast cancer cells

Maria J Silva, Anke Beckedorf, Erhard Bieberich

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Bone metastasis is the major reason for death caused by breast cancer. We used human breast cancer (MCF-7) cells that are poorly metastatic but show highly inducible migration to determine bone-derived factors that induce migration of initially non-disseminating breast cancer cells. We have found that a lipid fraction from human osteoblast-like MG63 cell-conditioned medium (MG63CM) contains a migration-inducing factor for MCF-7 cells. In this fraction, we have identified oxysterol (OS) as a lipid mediator for tumor cell migration. In MCF-7 cells, insulin-like growth factor 1 elevates the expression of OS-binding protein-related protein 7. Binding of OS to OS-binding protein or OS-binding protein-related protein is known to trigger elevation of sphingomyelin, a sphingolipid that organizes lipid microdomains in the cell membrane. In MCF-7 cells, OS increases the intracellular concentration of sphingomyelin and other phospholipids and induces the translocation of the small GTPase p21Ras to GM1- and cholesterol-rich membrane areas. The induction of migration by MG63CM is prevented by incubation of MG63 cells with mevinolin, a statin-type cholesterol biosynthesis inhibitor that depletes the conditioned medium of OS. Osteoblast-derived OS may, thus, be a yet unrecognized lipid mediator for bone metastasis of breast cancer and a new target for anti-metastasis chemotherapy with statins.

Original languageEnglish (US)
Pages (from-to)25376-25385
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number28
DOIs
StatePublished - Jul 11 2003

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Osteoblasts
MCF-7 Cells
Conditioned Culture Medium
Cells
Breast Neoplasms
Lipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Bone
Sphingomyelins
Neoplasm Metastasis
Bone and Bones
Cholesterol
Cell Movement
Lovastatin
Sphingolipids
Chemotherapy
Monomeric GTP-Binding Proteins
Anticholesteremic Agents
Biosynthesis
Somatomedins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Osteoblast-derived oxysterol is a migration-inducing factor for human breast cancer cells. / Silva, Maria J; Beckedorf, Anke; Bieberich, Erhard.

In: Journal of Biological Chemistry, Vol. 278, No. 28, 11.07.2003, p. 25376-25385.

Research output: Contribution to journalArticle

Silva, Maria J ; Beckedorf, Anke ; Bieberich, Erhard. / Osteoblast-derived oxysterol is a migration-inducing factor for human breast cancer cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 28. pp. 25376-25385.
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