Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis
Menée in vitro et in vivo, cette étude analyse les caractéristiques neuro-anatomiques et neuro-chimiques des cellules de rétinoblastome chez la souris et l'humain
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. º Human and mouse retinoblastomas tumors are relatively homogenous º Retinblastoma cells express multiple retinal developmental programs simultaneously º Retinoblastomas have neuroanatomical and neurochemical features of amacrine cells º Retinoblastomas may use monoamine neurotransmitters for autocrine mitogenic signaling
Cancer cell , résumé, 2010