A cranial invasion model of human neuroblastoma using congenitally athymic mice.

Even though the current limits of treatment for advanced stage neuroblastoma require an understanding of biology and new therapeutic approaches, few invasion models of human neuroblastoma (HNB) which evaluate experimental therapies have been reported. We describe herein a reproducible murine model of cranial invasion after the intraocular xenograft of HNB in congenitally athymic mice. Approximately 10 weeks after the intraocular injection of 5 x 10(6) NB-1 HNB cells, 70% (14/20) of the mice developed intracranial invasion with skull involvement. There was no operative mortality. Macroscopically, deformities of the cranium were revealed in all 14 mice, 5 of which developed exophthalmos. Microscopically, cranial invasion mainly involved the extradural space, skull, and orbita; however, brain involvement could not be seen, indicating that the dura may act as a barrier. These invasive characteristics are very similar to those seen in humans; thus, we believe that this model provides a useful tool for evaluating the biology of, and new therapeutic approaches against, cranial invasion of neuroblastoma in vivo.