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Abstract

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.

Internal radiotherapy of painful bone metastases

“…Although most tumor cells do not survive the protective host-surveillance mechanism in this initial stage [9,10], the surviving cells enter the bone marrow cavity [5] and are believed to adhere to the endothelium [11]. Tumor cells can then enter the bone and potentially form bone metastases, or the bone provides chemotactic factors to adhere the tumor cells [12,13]. Direct and indirect effects of the tumor on the vascular system ultimately cause necrosis and bone destruction [14].…”

“…In prostate cancer the balance between resorption and mineralization is impaired resulting in the overall formation of an osteoblastic lesion [12], but the resorption by osteoclast is not completely lost [11] since increased systemic markers of both bone formation and resorption have been observed in patients with prostate cancer [11]. Bone metastases caused by breast cancer are more mixed, comprising both osteolytic and osteoblastic elements.…”

Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone

“…The concept, which is presently accepted, is that PCa develops in the skeleton due to bidirectional and dynamic interaction between tumors and the bone microenvironment [1][2][3][4][5][6]. The bone microenvironment is a complex environment composed of a variety of cell types including osteoblasts, osteoclasts, endothelial cells, hematopoietic cells, and stromal cells.…”

Incidence of cancer of unknown primary in Sweden

“…This trend might be explained by the similar agespecific incidence for colorectal cancer (compare http:// www-dep.iarc.fr/NORDCAN/english/frame.asp) as this is known to be the most common primary site for liver metastasis at least in cancers other than CUP (Barugel et al, 2009). Similarly, the age-specific incidence trend for CUP with diagnosed bone metastasis can be explained by a similar age-specific incidence for prostate cancer with bone as most common metastatic site (Keller et al, 2001).…”

“…The most common metastatic site among prostate cancer patients is the bone (Keller et al, 2001). The decline of almost 60% in the incidence of CUP with bone metastasis within the last two periods may be attributed to improved methods for detection of prostate cancer as a primary tumor.…”