Mechanisms of tumor metastasis to bone

Bone metastases occur in approximately 80% of patients with advanced cancer. They are characterized by cancer cell growth and bone destruction that cause pain, fractures, anemia, and hypercalcemia. At diagnosis, bone metastases are usually incurable owing to their advanced development. However, the early stages in their formation are asymptomatic and begin as single micrometastatic cells from the blood stream. These cells can be detected by molecular analysis of bone marrow in approximately 30% of patients at the time of cancer diagnosis, but not all single micrometastatic cells develop into clinically significant bone metastases. A synergistic relationship exists between the micometastasis and the bone environment creating favorable conditions for the development and growth of disseminated tumor cells. Such bone metastases induce osteolysis or new bone formation, releasing growth factors and cytokines, which in turn amplify this pathological mechanism. The underling hypothesis, first proposed by Paget in 1889, is that the growth of disseminated tumor cells in bone is dependent on the fertility of the soil or bone itself. This article explores the most current opinions in this area of study and presents a comprehensive summary of the major factors involved.