A metastatic neuroblastoma model in SCID mice

Abstract

Neuroblastoma (NB), a neural crest derived tumor in children, shows a characteristic pattern of dissemination that includes adrenal glands, local lymph nodes, bone, liver, skin, and bone marrow. We have reconstructed a similar metastatic pattern in SCID mice following tail vein injection of human NB cells. HTLA230, an NB cell line isolated from a patient with advanced disease, and its NGF receptor (trkA) expressing derivative (18-10) cells, consistently disseminated to the liver, the adrenal gland, and the bone marrow, but not the lungs. Metastases in the different organs showed a characteristic hemorrhagic histopathology, and tumors in the bone marrow presented as syncytia-like cell aggregates, typically seen in patients. Cell lines reestablished from 18-10 derived liver and bone marrow metastases maintained their cellular morphology, growth behavior, N-myc overexpression, trkA expression, and functionally responded to NGF treatment, leading to growth arrest and neurite outgrowth. Hence circulating human NB cells in SCID mice show a similar organ-specific metastatic potential as seen in patients, independent of trkA expression.