Mechanisms of bone invasion and metastasis in human neuroblastoma.
Bone is the second most common site of metastasis in neuroblastoma. Over the last several years, our understanding of the mechanism of bone metastasis in neuroblastoma has significantly improved. Like breast cancer and myeloma, neuroblastoma cells activate osteoclasts to form osteolytic lesions. Activation occurs via the receptor activator of NFkappaB ligand (RANKL) or in the absence of RANKL via activation of bone marrow mesenchymal stem cells and stimulation by these cells of the expression of IL-6, a potent osteoclast activating factor. Several targets for therapeutic intervention can now be identified. Inhibition of osteoclast activation by bisphosphonates has already shown to be effective in preclinical models of neuroblastoma bone metastasis and should now be tested in phase I clinical studies. Inhibition of RANKL and IL-6 are other potential targets that require preclinical studies before being tested in patients. This article provides a review of our current understanding of the mechanisms involved in bone metastasis in neuroblastoma and discusses how this knowledge is leading to the identification of new targets for therapeutic intervention.
Division of Hematology-Oncology, Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
Yasuyoshi
Y
Sohara
Hiroyuki
H
Shimada
Yves A
YA
DeClerck
D001859:Bone Neoplasms / Q000556:secondary*; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000473:pathology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D002352:Carrier Proteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human