Abstract
Mechanisms leading to the development of virulent prostate cancer are not confined to the cancer epithelial cell, but also involve the tumor microenvironment. Multiple signaling pathways exist between epithelial cells, stromal cells, and the extracellular matrix to support tumor progression from the primary site to regional lymph nodes and distant metastases. Prostate cancers preferentially metastasize to the skeleton, prompting considerable research effort into understanding the unique interaction between prostate cancer epithelial cells and the bone microenvironment. This effort has led to the discovery that signaling pathways involved in normal prostate and bone development become dysregulated in cancer. These pathways stimulate excessive cell growth and neovascularization, impart more invasive properties to epithelial cells, weaken antitumor immune surveillance, and promote the emergence of castrate-resistant disease. An improved understanding of the complex relationship between cancer epithelial cells and the organ-specific microenvironments with which they interact has created a powerful opportunity to develop novel therapies.