Metastatic and nonmetastatic models of retinoblastoma

To generate animal models of retinoblastoma that closely resemble metastati c and nonmetastatic human disease for the purposes of examining tumor biolo gy and developing alternate treatments, human retinoblastoma cell lines wer e injected into the vitreal cavities of immunodeficient mice. Two reproduci ble animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrat ed specific tumor evolution similar to that seen in human invasive and meta static disease. Y79 retinoblastoma cells formed intraocular tumors that wer e initially con fined to the vitreal cavity. Tumors progressively invaded t he retina, subretinal space, choroid, optic nerve head, and anterior chambe r of the eye. Tumors progressed into the subarachnoid space and focally inv aded the brain. Metastases were detected in the contralateral optic nerve. Large tumors developed extraocular extensions. The histology of the tumors showed a poorly differentiated pattern with high mitotic rate, foci of necr osis, and calcification. The WERI-Rb, model more closely resembled nonmetas tatic human retinoblastoma WERI- Rb tumors were localized in the eye with o nly anterior choroidal invasion at late stages, To examine potential biolog ical differences in vitro, the retinoblastoma cell lines were cocultured wi th adherent choroid cells or adherent glioma cells which represent the targ ets of invasive retinoblastoma in vivo. Consistent with the in vivo observa tions,Y79 cells but not WERI-Rb cells adhere specifically to both the choro idal and the glioma cell lines.