Lytic bone lesions in human neuroblastoma xenograft involve osteoclast recruitment and are inhibited by bisphosphonate.
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.
Sohara
Yasuyoshi
Y
Department of Pediatrics, Division of Hematology-Oncology, Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA.
Shimada
Hiroyuki
H
Scadeng
Miriam
M
Pollack
Harvey
H
Yamada
Shinya
S
Ye
Wei
W
Reynolds
C Patrick
CP
DeClerck
Yves A
YA
D000311:Adrenal Glands; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D005266:Femoral Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D005269:Femur; D006321:Heart; D006801:Humans; D000077557:Ibandronic Acid; D007267:Injections; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D010010:Osteoclasts / Q000502:physiology*; D010014:Osteolysis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D013623:Tail / Q000098:blood supply; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D004164:Diphosphonates; D000077557:Ibandronic Acid