Lytic bone lesions in human neuroblastoma xenograft involve osteoclast recruitment and are inhibited by bisphosphonate

Cancer Res. 2003 Jun 15;63(12):3026-31.

Abstract

Neuroblastoma is the second most common solid tumor in childhood and frequently metastasizes to the bone marrow and the bone matrix. The mechanism involved in bone metastasis and destruction in neuroblastoma is poorly understood. Using a model of bone invasion in immunodeficient mice, we demonstrated that neuroblastoma cells recruited osteoclasts to generate osteolytic lesions and invade the bone matrix. In further support of a contributory role for osteoclasts in neuroblastoma bone invasion, we demonstrated that treatment with the bisphosphonate compound, ibandronate, significantly delayed the progression of osteolytic lesions. The data suggest that bisphosphonates may be clinically effective in the treatment of bone metastases in neuroblastoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands
  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms / complications
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Diphosphonates / therapeutic use*
  • Female
  • Femoral Neoplasms / complications
  • Femoral Neoplasms / drug therapy
  • Femoral Neoplasms / secondary*
  • Femur
  • Heart
  • Humans
  • Ibandronic Acid
  • Injections
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neuroblastoma / complications
  • Neuroblastoma / drug therapy
  • Neuroblastoma / secondary*
  • Osteoclasts / physiology*
  • Osteolysis / drug therapy
  • Osteolysis / etiology
  • Osteolysis / prevention & control*
  • Tail / blood supply
  • Tumor Cells, Cultured / pathology
  • Tumor Cells, Cultured / transplantation
  • Xenograft Model Antitumor Assays

Substances

  • Diphosphonates
  • Ibandronic Acid