Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis

Justina McEvoy, Jacqueline Flores-Otero, Jiakun Zhang, Katie Nemeth, Rachel Brennan, Cori Bradley, Fred Krafcik, Carlos Rodriguez-Galindo, Matthew Wilson, Shunbin Xiong, Guillermina Lozano, Julien Sage, Ligia Fu, Lotfi Louhibi, Jeff Trimarchi, Amar Pani, Richard Smeyne, Dianna Johnson, Michael A. Dyer

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)260-275
Number of pages16
JournalCancer Cell
Volume20
Issue number2
DOIs
StatePublished - Aug 16 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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