Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
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DOI:
10.1016/j.ccr.2011.07.005
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发表时间:
2011-08-16
期刊:
影响因子:
50.3
通讯作者:
Dyer MA
Dyer MA
中科院分区:
医学1区
文献类型:
--
作者:
McEvoy J;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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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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