Breast cancer metastasis to bone: Mechanisms of osteolysis and implications for therapy

Wende Kozlow, Theresa Guise

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

The most common skeletal complication of breast cancer is osteolytic bone metastasis. Bone metastases are present in 80% of patients with advanced disease and cause significant morbidity. They are most often osteolytic, but can be osteoblastic or mixed. Tumor cells, osteoblasts, osteoclasts and bone matrix are the four components of a vicious cycle necessary for the initiation and development of bone metastases. Tumor cell gene expression is modified by interaction with bone-derived factors. For example, parathyroid hormone related protein (PTHrP), a tumor cell factor, is upregulated by bone-derived transforming growth factor β (TGFβ). Tumor cell factors, in turn, act upon bone cells to cause dysregulated bone destruction and formation. PTHrP increases osteoblast expression of RANK (receptor activator of NFκB) ligand which, in turn, activates osteoclasts. PTHrP-independent osteolytic factors, such as interleukin [IL]-11 and IL-8, also contribute to the vicious cycle. Other tumor-bone interactions, such as stimulation of tumor-homing through the CXCR4 chemokine receptor by its bone-derived ligand stromal-derived factor-1 (SDF-1), may be responsible for the site-specific predilection of breast cancer for bone. These factors and their roles in fueling the vicious cycle may identify novel targets for therapies to prevent metastasis.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalJournal of Mammary Gland Biology and Neoplasia
Volume10
Issue number2
DOIs
StatePublished - Apr 2005
Externally publishedYes

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Osteolysis
Breast Neoplasms
Neoplasm Metastasis
Parathyroid Hormone-Related Protein
Bone and Bones
Neoplasms
Osteoclasts
Osteoblasts
Therapeutics
Interleukin-11
CXCR4 Receptors
Ligands
Bone Neoplasms
Bone Matrix
Chemokine Receptors
Bone Development
Interleukin-8
Osteogenesis
Transforming Growth Factor beta
Morbidity

Keywords

  • Bone metastasis
  • Osteolytic metastasis
  • Parathyroid hormone-related protein
  • Skeletal-related event

ASJC Scopus subject areas

  • Cancer Research

Cite this

Breast cancer metastasis to bone : Mechanisms of osteolysis and implications for therapy. / Kozlow, Wende; Guise, Theresa.

In: Journal of Mammary Gland Biology and Neoplasia, Vol. 10, No. 2, 04.2005, p. 169-180.

Research output: Contribution to journalArticle

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