Bone morphogenetic protein and bone metastasis, implication and therapeutic potential

Front Biosci (Landmark Ed). 2011 Jan 1;16:865-97. doi: 10.2741/3725.

Abstract

Bone metastasis is one of the most common and severe complications in advanced malignancies, particularly in the three leading cancers; breast cancer, prostate cancer and lung cancer. It is currently incurable and causes severe morbidities, including bone pain, hypercalcemia, pathological fracture, spinal cord compression and consequent paralysis. However, the mechanisms underlying the development of bone metastasis remain largely unknown. Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily and are pluripotent factors involved in the regulation of embryonic development and postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Since they are potent regulators for bone formation, there is an increasing interest to investigate BMPs and their roles in bone metastasis. BMPs have been implicated in various neoplasms, at both primary and secondary tumors, particularly skeletal metastasis. Recently studies have also suggested that BMP signaling and their antagonists play pivotal roles in bone metastasis. In this review, we discuss the current knowledge of aberrations of BMPs which have been indicated in tumor progression, and particularly in the development of bone metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgens / physiology
  • Apoptosis / drug effects
  • Bone Morphogenetic Protein Receptors / physiology
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / physiology*
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • DNA Methylation
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Humans
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic
  • Osteoblasts / physiology
  • Osteolysis / physiopathology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Estrogen / physiology
  • Signal Transduction / physiology*
  • Smad Proteins / physiology

Substances

  • Androgens
  • BAMBI protein, human
  • Bone Morphogenetic Proteins
  • Membrane Proteins
  • Receptors, Estrogen
  • Smad Proteins
  • Bone Morphogenetic Protein Receptors