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D. Cobrinik, X. L. Xu, N. L. Offor, A. H. Liu, T. C. Lee, D. H. Abramson; Rb(+) Astrocyte-Like Cells Support Retinoblastoma Cell Growth and Survival. Invest. Ophthalmol. Vis. Sci. 2008;49(13):19.
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Retinoblastoma is a childhood eye cancer that forms due to the mutation of RB1 and loss of Rb protein. In addition to the neoplastic cells, retinoblastomas contain non-neoplastic cells whose roles in tumorigenesis are undefined. Here, we investigated the derivation and role of glial cells that are present in virtually all retinoblastoma tumors.
Retinoblastoma glia were characterized by staining for GFAP, CRALBP, vimentin, Sox2, and the retinal astrocyte marker Pax2. Their proliferative status was assessed by co-staining for Ki67 and their neoplastic status evaluated by co-staining for Rb. Glia were derived from explanted human retinoblastomas or from post-natal day 7 mouse retinas, and evaluated for the same glial markers. They were then assessed for effects on co-cultured neoplastic tumor cells by cell counting, Ki67 expression, and TUNEL staining.
Most of the tumor cells that express glial markers were Rb+, consistent with their being non-neoplastic. Many Rb+ glia expressed the stem cell marker Sox2 and the proliferation marker Ki67, indicating that they proliferate together with the neoplastic retinoblastoma cells. Glia were commonly positioned adjacent to the tumor vasculature, had cytoplasmic processes extending throughout the tumors, and expressed the retinal astrocyte marker Pax2, consistent with a retinal astrocyte identity. Because of the close apposition of Rb+ glia and Rb(-) neoplastic cells, we examined whether the retinoblastoma glia affect tumor cell growth. Adherent Pax2+ and GFAP+ cells grew from explanted retinoblastomas, but partially down-regulated Pax2+ and GFAP+ expression over 1-2 weeks. Tumor glia from three different tumors significantly increased proliferation, Ki67 staining, and survival of co-cultured neoplastic retinoblastoma cells. Normal mouse retinal glial cells had a similar effect.
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