Metastatic and nonmetastatic models of retinoblastoma

Patricia Chévez-Barrios, Mary Y. Hurwitz, Kathryn Louie, Karen T. Marcus, Vien N. Holcombe, Pamela Schafer, C. Estuardo Aguilar-Cordova, Richard Hurwitz

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor evolution similar to that seen in human invasive and metastatic disease. Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreal cavity. Tumors progressively invaded the retina, subretinal space, choroid, optic nerve head, and anterior chamber of the eye. Tumors progressed into the subarchnoid space and focally invaded 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 necrosis, and calcification. The WERI-Rb model more closely resembled nonmetastatic human retinoblastoma WERI- Rb tumors were localized in the eye with only anterior choroidal invasion at late stages. To examine potential biological differences in vitro, the retinoblastoma cell lines were cocultured with adherent choroid cells or adherent glioma cells which represent the targets of invasive retinoblastoma in vivo. Consistent with the in vivo observations, Y79 cells but not WERI-Rb cells adhere specifically to both the choroidal and the glioma cell lines.

Original languageEnglish (US)
Pages (from-to)1405-1412
Number of pages8
JournalAmerican Journal of Pathology
Volume157
Issue number4
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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