Genetics, Development and Cell Biology
Journal or Book Title
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.
McEvoy, Justina; Flores-Otero, Jacqueline; Zhang, Jiakun; Nemeth, Katie; Brennan, Rachel; Bradley, Cori; Krafcik, Fred; Rodriguez-Galindo, Carlos; Wilson, Matthew; Xiong, Shunbin; Lozano, Guillermina; Sage, Julien; Fu, Ligia; Louhibi, Lotfi; Trimarchi, Jeff; Pani, Amar; Smeyne, Richard; Johnson, Dianna; and Dyer, Michael A., "Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis" (2011). Genetics, Development and Cell Biology Publications. 88.