Introduction

Prostate cancer is the most common malignant tumor among men in the USA: more than 40 000 die of the disease annually.1 It is the most prevalent tumor in men and, despite increasing efforts at early detection, 10-20% of the cases present bone metastases at diagnosis. Most deaths from the disease are still caused by widespread metastases that are resistant to conventional treatment in spite of improved surgical techniques and local and systemic therapies. Bone is one of the common metastatic sites of malignant neoplasms, including those from carcinoma of the breast, prostate, thyroid, kidney and lung. Normal bone is continuously being remodeled with new bone formation by osteoblasts and bone degradation by osteoclasts; at bone metastatic sites, however, fine balance between the two processes is disturbed. When bone destruction dominates, net loss of bone mass occurs and the lesion is described as osteolytic; when an excessive amount of new bone formation takes place with less bone destruction, the lesion is described as osteoblastic or osteosclerotic. Human prostate cancer is one of the rare cancers that consistently produces osteoblastic metastasis to bone in approximately 95% of cases. Several growth factors including transforming growth factor (TGFP)2, basic fibroblast growth factor (bFGF)3 and bone morphogenetic protein (BMP)4, which stimulate osteoblast growth and bone matrix formation, are known in benign and malignant prostate cells.

The molecular basis for tumor progression, invasion and metastasis is still unclear, although recent reports have emphasized the importance of secreted proteases, cellular molecules,5 and the presence of mitogenic and angiogenic growth factors at the site of tumors, including at that of prostate cancer.5-8

In this chapter, we describe the general mechanism of cancer invasion and metastasis, and discuss the relationship between cancer cells, including prostatic carcinoma, and host stromal cells in cancer growth, invasion and metastasis. We then focus on the mechanism of and consider several growth factors related to osteoblastic metastasis from prostate cancer.

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