title: Role of TGF-βin breast cancer bone metastases.
abstract: Breast cancer is the most prevalent cancer among females worldwide leading to approximately 350,000 deaths each year. It has long been known that cancers preferentially metastasize to particular organs, and bone metastases occur in ~70% of patients with advanced breast cancer. Breast cancer bone metastases are predominantly osteolytic and accompanied by increased fracture risk, pain, nerve compression and hypercalcemia, causing severe morbidity. In the bone matrix, transforming growth factor-β(TGF-β) is one of the most abundant growth factors, which is released in active form upon tumor-induced osteoclastic bone resorption. TGF-β, in turn, stimulates bone metastatic tumor cells to secrete factors that further drive osteolytic bone destruction adjacent to the tumor. Thus, TGF-βis a crucial factor responsible for driving the feed-forward vicious cycle of cancer growth in bone. Moreover, TGF-βactivates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-βsignaling pathway to interrupt this vicious cycle between breast cancer and bone offers a promising target for therapeutic intervention to decrease skeletal metastasis. This review will describe the role of TGF-βin breast cancer and bone metastasis, and pre-clinical and clinical data will be evaluated for the potential use of TGF-βinhibitors in clinical practice to treat breast cancer bone metastases.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Chiechi
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Waning
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Stayrook
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA ; Department of Urology, Medical Center, Leiden University, Leiden, The Netherlands.
authors.forename: Jeroen T
authors.initials: JT
authors.lastname: Buijs
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Guise
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Indiana University, Indianapolis, USA.
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Mohammad
keywords: Antibodies; Bone; Bone Metastasis; Bone Resorption; Breast Cancer; Small Molecule Inhibitors; TGF-β; Transforming Growth Factor-Beta