Roles of Osteonectin in Breast Cancer Metastasis to Bone.

摘要

The focus of this study is to gain insight into the role(s) of osteonectin in the preferential metastasis of breast cancer cells to bone. Osteonectin was isolated from conditioned media of several cell lines including breast cancer (MDA-MB-435, MDA-MB-468), osteoblasts (hFOB1.19), non-neoplastic breast epithelial (hTERT-HME1), and vascular endothelial cells isolated from bone biopsies (HBME-1). Analysis of translational and post-translational properties of osteonectin from these five sources revealed that a unique configuration of the protein does not exist; thus there is no detectable chemotactic isoform. Osteonectin increased motility of the breast cancer cells (MDA-MB-231) on culture plate surfaces. However, in transwell migration assays the MDA-MB-231 cells were not attracted to bone-derived osteonectin. Bone extracts from both wild-type and osteonectin-null mice had a profound stimulatory effect on migration in transwell chambers. We conclude that osteonectin does not stimulate breast cancer migration and therefore is not a chemotactic factor in the development of skeletal metastases. However, osteonectin enhances random undirected motility of breast cancer cells and therefore likely has a supportive role in breast cancer metastasis.