Abstract
Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.
Highlights
Despite significant advances in our understanding of the molecular and cellular changes involved in the initiation and progression of cancer, there has not been a substantial reduction in proportionate cancer deaths
While only 4% of men with prostate cancer have metastatic disease, the presence of metastases portends a poor prognosis with a five-year survival rate of 30% [4]
As clinical detection and management of locoregional prostate cancer has become more sophisticated, research attention has shifted to its metastasis
Summary
Despite significant advances in our understanding of the molecular and cellular changes involved in the initiation and progression of cancer, there has not been a substantial reduction in proportionate cancer deaths. 12 million new cancer cases and 7.6 million deaths worldwide [1]. Ninety percent of these deaths can be attributed to metastatic disease, which is typically difficult to cure by conventional therapies (surgery, radiation and chemotherapy) [2]. These dismal statistics are largely due to the challenges posed by the complexity and heterogeneity of metastatic carcinomas, especially with regard to tumor dissemination and organ-specific colonization. Prostate cancer is the most commonly diagnosed noncutaneous cancer, and the second most common cause of cancer-related death among men in the United States. In 2010, an estimated 217,730 men will receive a diagnosis of prostate cancer, with an estimated lifetime disease incidence of 20% [3]
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