The development of bone metastasis is an organized multi-step process in which some organs are preferential targets. In patients with advanced cancer, bone is the third most common site for metastases after lung and liver. Some cancers are particularly osteophilic, such as cancers of the breast and prostate where bone metastases occur in 60 to 70% of patients. Bone metastases occurrence can be explained by the expression of different malignant factors such as the chemokine receptors CXCR4 or CX3CR1, or the integrin αVβ3 promoting cancer cell homing to bone. Another critical parameter of tumor cell development in bone is their ability to survive and grow in the bone microenvironment. Cancer cells (the seeds) arriving in the bone marrow cavity will not grow if they are not properly responsive or adapted to the bone environment (the soil). Bone is a unique and rich environment whose integrity relies on the balance between osteoclastic bone resorption and osteoblastic bone formation to renew and adapt. The arrival of tumor cells and their interactions with bone cells disrupts normal bone remodeling causing abnormal new bone formation or bone destruction that characterizes osteoblastic and osteolytic metastases, respectively. Osteoblastic metastases are common with advanced prostate cancer while breast cancer bone metastases are typically osteolytic. However, many bone metastases are mixed and contain both osteoblastic and osteolytic characteristics. These skeletal complications have significant clinical consequences (hypercalcemia, intractable pain, fractures, nerve compression syndromes) that reduce the quality of life of these patients. More importantly, unbalanced bone remodeling provides metastatic tumor cells the means to grow and survive in bone.
|Original language||English (US)|
|Title of host publication||Bone Cancer|
|State||Published - Dec 1 2010|
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