TGF-β Signaling in Bone Remodeling and Osteosarcoma Progression

Abstract

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-β (TGF-β), which in turn promote tumor progression. Over the past years, there has been considerable interest in the TGF-β pathway within the cancer research community. This review discusses the involvement of the TGF-β signalling pathway in osteosarcoma development and in their metastatic progression.

Long Non-Coding RNA Urothelial Carcinoma Associated 1 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Regulating microRNA-182

“…TGF-β and TNF-α have been demonstrated to play tumor promoting roles in osteosarcoma [45,46]. So, in the current study, we further assessed the effects of UCA1 on p53, Rb, iASPP and RECQL, as well as the effects of TGF-β and TNF-α on UCA1 in OS-732 cells.…”

Cancer stem cells in osteosarcoma

“…Sphere cells had increased stem like factor and ABC transporter expression levels, increased resistance to cisplatin and adriamycin and in vivo tumour formation. The role of TGF in general tumour progression was widely studied and its role in osteosarcoma suspected (40). !Indeed, the relevance of TGFβ1 to propagate a stem like phenotype in osteosarcoma was shown when inhibition of the TGFβ1-receptor resulted in reduced sphere formation.…”

Immunotherapy for osteosarcoma: Where do we go from here?

“…Transforming growth factor‐beta (TGF‐β) is a growth factor present in the tumor microenvironment of osteosarcoma that stimulates tumor growth . The expression of TGF‐β is higher in patients with osteosarcoma than that in healthy individuals, higher in metastatic disease versus localized disease, and correlates with a lack of response to chemotherapy . Preclinical osteosarcoma murine models showed antitumor effects when TGF‐β blockade was combined with DC, due to immune response reconstitution .…”