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Steve Brocchini, Maayke Kuijten, Annegret Dahlmann-Noor, Peng Khaw; Differentiation of retinoblastoma cancer stem cells as in vitro model of optic nerve. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2236.
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Retinoblastoma (RB) is a malignant tumour of the developing retina and is the most common eye cancer in children. Cancer stem cells (CSCs) have recently been discovered in different cancers, including retinoblastoma, and evidence is increasing that these cells express neuronal stem cell markers. In this study we investigate whether the CSCs can express neuronal as well as retinal related markers and whether CSCs are able to differentiate into retinal ganglion-like cells which could be used as an in vitro model to help in developing new treatment for optic nerve protection.
We used the Y79 and WERI-Rb1 cell lines (a kind gift from Prof Ohnuma) as an in vitro model for retinoblastoma. Immunocytochemistry was used to detect cancer stem cells with different markers including CD44, nestin, ABCG2, Sox2 and Pax6. The CSCs were expanded using serum-free culture conditions and were differentiated into neuron-like cells using γ-secretase, retinoic acid and Wnt inhibitors. Differentiation of the CSCs was assessed based on neuronal and retinal ganglion cell specific markers using molecular biology techniques such as immunocytochemistry.
Retinoblastoma cell lines Y79 and WERI-Rb1 contain a subpopulation of cancer stem cells. Under special serum-free culture conditions the cancer stem cells can be expanded into neurosphere-like spheres. These cancer stem cells can be differentiated into more retinal ganglion-like cells using the γ-secretase inhibitor DAPT, retinoic acid and Wnt inhibitor Dickkopf-related protein 1 (Dkk1). The differentiated cells express retinal ganglion cell markers and neuronal markers to an apparent higher extent when compared to the undifferentiated CSCs and undifferentiated cancer cells.
Cancer stem cells form a subpopulation in retinoblastoma and seem to be able to differentiate into more retinal ganglion-like cells based on marker expression and cell morphology. These differentiated cells have the potential to be used as an in vitro model to develop treatments to preserve the optic nerve.
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