TGF-β in the bone microenvironment: Role in breast cancer metastases

Jeroen T. Buijs, Keith R. Stayrook, Theresa A. Guise

Research output: Contribution to journalReview article

48 Scopus citations


Breast cancer is the most prevalent cancer among females worldwide. 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 bone destruction, bone fractures, pain, and hypercalcemia, causing severe morbidity and hospitalization. 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 cells to secrete factors that further drive osteolytic destruction of the bone adjacent to the tumor, categorizing TGF-β as a crucial factor responsible for driving the feedforward 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.

Original languageEnglish (US)
Pages (from-to)261-281
Number of pages21
JournalCancer Microenvironment
Issue number3
StatePublished - Dec 1 2011


  • Antibodies
  • Bone
  • Bone metastasis
  • Bone resorption
  • Breast cancer
  • Small molecule inhibitors
  • TGF-β
  • Transforming growth factor-beta

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'TGF-β in the bone microenvironment: Role in breast cancer metastases'. Together they form a unique fingerprint.

  • Cite this