TITLE:
Role of TGF-β in breast cancer bone metastases
AUTHORS:
Antonella Chiechi, David L. Waning, Keith R. Stayrook, Jeroen T. Buijs, Theresa A. Guise, Khalid S. Mohammad
KEYWORDS:
Transforming Growth Factor-Beta; TGF-β; Breast Cancer; Bone Metastasis; Bone; Small Molecule Inhibitors; Antibodies; Bone Resorption
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.10C,
October
18,
2013
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-β is a crucial factor responsible for driving the feed-forward vicious cycle of cancer
growth in bone. Moreover, TGF-β activates epithelial-to-mesenchymal transition, increases tumor cell invasiveness and angiogenesis and induces immunosuppression. Blocking the TGF-β signaling 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-β in breast cancer and bone metastasis,
and pre-clinical and clinical data will be evaluated for the potential use of
TGF-β inhibitors in clinical practice
to treat breast cancer bone metastases.