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

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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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
Pages (from-to)261-281
Number of pages21
JournalCancer Microenvironment
Volume4
Issue number3
DOIs
StatePublished - Dec 2011

Fingerprint

Transforming Growth Factors
Bone Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Neoplasms
Growth Inhibitors
Bone Matrix
Epithelial-Mesenchymal Transition
Bone Development
Bone Fractures
Hypercalcemia
Bone Resorption
Immunosuppression
Intercellular Signaling Peptides and Proteins
Hospitalization
Morbidity
Pain

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

TGF-β in the bone microenvironment : Role in breast cancer metastases. / Buijs, Jeroen T.; Stayrook, Keith R.; Guise, Theresa.

In: Cancer Microenvironment, Vol. 4, No. 3, 12.2011, p. 261-281.

Research output: Contribution to journalArticle

Buijs, Jeroen T. ; Stayrook, Keith R. ; Guise, Theresa. / TGF-β in the bone microenvironment : Role in breast cancer metastases. In: Cancer Microenvironment. 2011 ; Vol. 4, No. 3. pp. 261-281.
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