Osteoblast-Derived Factors Induce an Expression Signature that Identifies Prostate Cancer Metastasis and Hormonal Progression

¹Genome Sciences Centre and ²Cancer Endocrinology, British Columbia Cancer Agency, ³Department of Urology, University of Washington, and ⁴Orthopaedic Surgery Vancouver General Hospital, Vancouver, British Columbia, Canada

^* To whom correspondence should be addressed. E-mail: msadar{at}bcgsc.ca.

	Abstract

Identification of gene expression signatures associated with metastases provides a tool to discern mechanisms and potential therapeutic targets and may lead toward a molecular classification system in pathology. Prostate cancer (CaP) frequently metastasizes to the bone to form osteoblastic lesions. Correlative clinical data and in vitro evidence have led to the hypothesis that osteoblast-derived factors promote hormonal progression of CaP cells. Here, the gene expression signature of CaP exposed to osteoblast-derived factors was identified. This signature included known androgen-regulated genes, oncogenes, tumor suppressors, and genes whose products are involved in apoptosis and cell cycle. A comparative functional genomic approach involved the application of this responsive gene expression signature to clinical samples of human CaP, melanomas, and oral cancers. Cluster analysis revealed that this gene expression signature had specificity for CaP and could resolve clinical specimens according to stage (benign, localized, and metastatic) and androgen sensitivity with an accuracy of 100% and 80%, respectively. Together, these results suggest that factors derived from osteoblasts induce a more advanced phenotype of CaP and promotes hormonal progression. [Cancer Res 2009;69(8):3433–42]

Key Words: bone metastases, hormonal progression, prostate cancer