Physiopathologie des métastases osseuses des tumeurs solides

Abstract

Bone metastases are frequent complications of many cancers. As regards pathophysiology, mechanisms that arise before the occurrence of bone metastases involve steps that are the same in all metastasis types (setting up of a pre-metastatic niche, chimiotactism and invasion of tumor cells in host tissues) but also require distinct bone-specific steps (settlement of tumor cells in the bone marrow, osteomimicry). After tumor cells in the bone marrow stay latent (dormancy) for a period of time that could last several years, they may exit from dormancy for outgrowth, at which time they disrupt bone remodeling by altering normal osteoclast and osteoblast functions. This leads to the formation of osteolytic (excess of bone destruction), osteosclerotic (excess of bone formation) or mixed bone lesions. Bone metastases are osteolytic as a consequence of the stimulation of osteoclast activity by tumor cells, whereas osteoblast activity is inhibited. Conversely, the stimulation of osteoblast activity and inhibition of osteoclast activity by tumor cells leads to the formation of osteosclerostic lesions. Furthermore, the mineralized bone matrix plays an important role in the formation of bone metastases. Disruption of bone remodeling causes the release of matrix-stored growth factors and calcium that stimulate tumor growth. Thus, there is a vicious cycle whereby tumor cells disrupt bone remodeling and resorbed bone promotes tumor growth.