Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer
Abstract
A clinically relevant syngeneic model of breast cancer metastasis has been used to determine gene expression alterations that occur both between primary breast cancers with varying metastatic potential and between matched primary and bone metastases. We have immunopurified epithelial and endothelial cell populations and profiled them separately to identify differentially expressed genes, some of which have not previously been associated with breast cancer metastasis. Expression profiles of vascular endothelium derived from primary tumors of varying metastatic potential identified aberrant expression of genes involved in angiogenesis, cell cycle progression, cytoskeletal structure and tumor suppression. Those altered in the primary tumor epithelium included developmental genes, metastasis suppressors and genes involved in cytoskeletal organization, cell cycle progression, apoptosis and transformation. The microarray data was confirmed by quantitative RT-QPCR. Further analysis of epithelium from matched spine metastases revealed some genes that were upregulated further at the metastatic site. These included stefin Al (inhibitor of cathepsin S) that was upregulated in highly metastatic primary epithelium and increased a further 9-fold in matched bone metastases. The expression in spine metastases was verified by in situ hybridization whilst the expression of stefin Al in subsets of tumor cells in invasive human breast cancer was confirmed by immunohistochemistry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428930
Entities
People
- Belinda S. Parker
- Robin L. Anderson
Organizations
- University of Melbourne