mechanism of induction of migration of breast cancer cells into bone

Unfortunately done on MDA MB231 cells--her2 breast cancer may use a different pathway, but interesting nonetheless. I previously posted on gugglesterone about a week ago

1: J Lipid Res. 2006 Jan 26; [Epub ahead of print] Links

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

Silva J, Dasgupta S, Wang G, Krishnamurthy K, Ritter E, Bieberich E.

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.

PMID: 16439808 [PubMed - as supplied by publisher]