Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
Cancer Cell, 2011/8/16;20(2):260-75.
McEvoy J[1], Flores-Otero J, Zhang J, Nemeth K, Brennan R, Bradley C, Krafcik F, Rodriguez-Galindo C, Wilson M, Xiong S, Lozano G, Sage J, Fu L, Louhibi L, Trimarchi J, Pani A, Smeyne R, Johnson D, Dyer MA
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PMID: 21840489DOI: 10.1016/j.ccr.2011.07.005
Impact factor: 38.585
Abstract
It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro.
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