Journal Article

The Role of TGF-β in Bone Metastases

Guise, Theresa A., Mohammad, Khalid S., Pagnotti, Gabriel M., Trivedi, Trupti

2021

Overview

Complications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is unique, providing fertile soil for cancer cell propagation, while mineralized bone matrices store potent growth factors and cytokines. Biologically active transforming growth factor β (TGF-β), one of the most abundant growth factors, is released following tumor-induced osteoclastic bone resorption. TGF-β promotes tumor cell secretion of factors that accelerate bone loss and fuel tumor cells to colonize. Thus, TGF-β is critical for driving the feed-forward vicious cycle of tumor growth in bone. Further, TGF-β promotes epithelial-mesenchymal transition (EMT), increasing cell invasiveness, angiogenesis, and metastatic progression. Emerging evidence shows TGF-β suppresses immune responses, enabling opportunistic cancer cells to escape immune checkpoints and promote bone metastases. Blocking TGF-β signaling pathways could disrupt the vicious cycle, revert EMT, and enhance immune response. However, TGF-β’s dual role as both tumor suppressor and enhancer presents a significant challenge in developing therapeutics that target TGF-β signaling. This review presents TGF-β’s role in cancer progression and bone metastases, while highlighting current perspectives on the therapeutic potential of targeting TGF-β pathways.

• Publisher: MDPI AG,MDPI
• Subject: Angiogenesis / Animals / Apoptosis / Biological activity / Bone cancer / Bone growth / Bone loss / bone metastases / Bone Neoplasms - metabolism / Bone Neoplasms - pathology / Bone Neoplasms - secondary / Bone resorption / Bone tumors / Bones / Breast cancer / Cancer therapies / Cell death / check-point inhibitors / Clinical trials / Collagen / Cytokines / Epithelial-Mesenchymal Transition / Extracellular matrix / Growth factors / Homeostasis / Hormones / Humans / Hydroxyapatite / immune cells / Immune checkpoint / Immune response / Immunotherapy / Invasiveness / Kinases / Medical prognosis / Mesenchyme / Metastases / Metastasis / Microenvironments / Minerals / Morbidity / Osteoclasts / Phosphatase / programmed cell death ligand (PD-L1) / Prostate cancer / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - pathology / Proteins / Review / Signal Transduction / TGF-β therapeutic targets / Transforming Growth Factor beta - metabolism / Transforming growth factor-b / transforming growth factor-β (TGF-β) / Tumor cells / Tumor Microenvironment / Tumor suppressor genes