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D.A. Johnson, M.A. Dyer; Differentiation and Dendrite/Synapse Formation in Retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4204.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this research project is to characterize the different types of cells in human and mouse retinoblastoma. This characterization will help us to determine if there are two populations of cells, cancer stem cells and differentiated retinoblastoma tumor cells.
We performed immunostaining and EM analysis of human retinoblastomas and mouse retinoblastomas from several different genetic combinations. These include tumors that arise from Rb,p107, Rb, p130 and Rb,p107,p53 deficient retinal progenitor cells. In addition, we characterized both early and late stage tumors including invasive tumor regions for distinct tumor cell populations. Finally, golgi staining was carried out to visualize the dendritic morphology of differentiated tumor cells.
We report here for the first time that mouse retinoblastoma cells differentiate with neuronal properties. They extend dendrites and form synaptic structures characterized by synaptic densities and synaptic vesicles. Based on the EM analysis these structures are consistent with amacrine or horizontal cell differentiation. Immunostaining confirmed the expression of proteins involved in amacrine/horizontal cell synapse formation as well as retinal progenitor specific genes. The golgi staining was consistent with amacrine/horizontal cell differentiation. Importantly, we noted regionalization of the tumor with some more densely packed regions of the tumor lacking this differentiation phenotype. The more aggressive tumors such as those in Rb,p107,p53 deficient retinae had fewer differentiated regions compared to the Rb,p107 deficient tumors.
These data demonstrate that the retinoblastoma tumors differentiate and even form extensive dendritic structures and synaptic connections. We propose that this is characteristic of early stage tumorigenesis and as the tumors progress to the more aggressive invasive form of retinoblastoma they lose this property.
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