TGF-β Signaling in Bone Remodeling and Osteosarcoma Progression

Osteosarcomas are the most prevalent malignant primary bone tumors in children. Despite intensive efforts to improve both chemotherapeutics and surgical management, 40% of all osteosarcoma patients succumb to the disease. Specifically, the clinical outcome for metastatic osteosarcoma remains poor; less than 30% of patients who present metastases will survive five years after initial diagnosis. Treating metastatic osteosarcoma thus remains a challenge. One of the main characteristics of osteosarcomas is their ability to deregulate bone remodelling. The invasion of bone tissue by tumor cells indeed affects the balance between bone resorption and bone formation. This deregulation induces the release of cytokines or growth factors initially trapped in the bone matrix, such as transforming growth factor- (TGF-), which in turn promote tumor progression. Over the past years, there has been considerable interest in the TGF- pathway within the cancer research community. This review discusses the involvement of the TGF- signalling pathway in osteosarcoma development and in their metastatic progression.