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.
Highlights
Bone is the most common site to which breast cancer cells metastasize
Using the agarose drop coculture migration assay that was developed in our laboratory [3], we observed that MDA-MB-231 cells were attracted to fragments of living human bone tissue placed into the tissue culture dish with Vybrant-CM diI-labeled breast cancer cells embedded in agarose (Fig. 1A)
Induction of migration resulted in the attachment of MDA-MBA-231 cells to cells within the bone tissue, suggesting that a migration-inducing lipid contributed to the homing of metastatic breast cancer cells into the bone
Summary
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). Breast cancer cell migration by human bone-derived lipids 725 protocol. Cholesterol derivatives from human bone tissue and MG63-CM induce the migration of MDA-MB-231 cells
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