Establishment and characterization of xenograft models of human neuroblastoma bone metastasis.

OBJECTS

To improve the therapy of advanced neuroblastoma (NB), it is critical to develop animal models that mimic NB bone metastases. Unlike the human disease, NB xenograft models rarely metastasize spontaneously to bone from the orthotopic site of primary tumor growth.

METHODS

Single-cell suspensions of SY5Y, KCNR NB cells were injected directly into the femur of nude mice. Radiological and histological analyses and immunohistochemistry analyses were performed to characterize these osseous NB models. SY5Y and KCNR result in osteolytic responses.

RESULTS

We have detected osteoprotegerin, receptor activator of nuclear factor kappa B ligand, parathyroid hormone-related protein, and endothelin-1, proteins associated with bone growth and osteolysis, and C-X-C chemokine receptor type 4 (CXCR4) involved in tumor growth and tumor cell migration in the NB cells grown in the bone.

CONCLUSIONS

These animal models can be used to study biological interactions, pathways, and potential therapeutic targets and also to evaluate new agents for treatment and prevention of NB bone metastasis.