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Clinical & Experimental Metastasis

, Volume 24, Issue 8, pp 599–608 | Cite as

Bone metastasis: pathogenesis and therapeutic implications

  • Philippe Clezardin
  • Anna Teti
Research Paper

Abstract

Advanced cancers are prone to metastasize. Visceral metastases are more likely to be fatal, while patients with only metastases to bone can survive up to 10 years or more. However, effective treatments for bone metastases are not yet available and bisphosphonates improve the quality of life with no life-prolonging benefits. Bone metastases are classified as osteolytic, osteosclerotic or mixed lesions according to the bone cell types more prominently involved. Either conditions induce high morbidity and dramatically increase the risk of pathological fractures. Several molecular mechanisms bring about cancer cells to metastasize to bone, and osteotropic cancer cells are believed to acquire bone cell-like properties which improve homing, adhesion, proliferation and survival in the bone microenvironment. The acquisition of a bone cell pseudo-phenotype, denominated osteomimicry, is likely to rely on expression of osteoblastic and osteoclastic genes, thus requiring a multigenic programme. Several microenvironmental factors improve the ability of cancer cells to develop at skeletal sites, and a reciprocal deleterious stimulation generates a vicious cycle between the tumour cells and the cells residing in the bone environment. The impact of the stem cell niche in the development of bone metastases and in the phenomenon of tumour dormancy, that allows tumour cells to remain quiescent for decades before establishing overt lesions, is at present only speculative. However, the osteoblast niche, known to maintain the haematopoietic stem cell population in a quiescent status, is likely to be involved in the development of bone metastases and this promising research field is rapidly expanding.

Keywords

Bone Breast Cancer Metastasis Osteolysis Osteoblast Osteoclast Prostate cancer 

Abbreviations

BMP

Bone morphogenetic protein

BSP

Bone sialoprotein

CDH11

Cadherin 11

Cox-2

Cycloxygenase 2

CXCL-12

Chemokine (C-X-C motif) ligand 12

CXCR4

Chemokine (C-X-C motif) receptor 4

Cx43

Connexin 43

DKK-1

Dickkopf

FGF

Fibroblast growth factor

MSX2

Homeo box homolog 2

OPG

Osteoprotegerin

PDGF

Platelet derived growth factor

PTHrP

Parathyroid hormone related peptide

RANK

Receptor activator of nuclear factor-κB

RANKL

Receptor activator of nuclear factor-κB ligand

Runx2

Runt-related transcription factor 2

SNO

Spindle-shaped N-cadherin positive osteoblast

SPARC

Secreted protein, acidic, cysteine-rich (osteonectin)

TGFβ

Transforming growth factor β

VEGF

Vascular endothelial growth factor

Wnt

Wingless-type protein-1

Notes

Acknowledgements

The original work was supported by the EU (MetaBre # LSHM-CT-2003-503049, to PC and AT), by the Associazione Italiana per la Ricerca sul Cancro (AIRC, to AT), the American Society for Bone and Mineral Research 2006 Bridge Funding Grant Award (to AT), and the Agence Nationale de la Recherche (GenHomme # 03 L 271, to PC).

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© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  1. 1.INSERM, Research Unit 664Laennec School of MedicineLyonFrance
  2. 2.Department of Experimental MedicineUniversity of L’AquilaL’AquilaItaly

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