Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.
Publication/Presentation Date
8-16-2011
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.
Volume
20
Issue
2
First Page
260
Last Page
275
ISSN
1878-3686
Published In/Presented At
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, M. A. (2011). Coexpression of normally incompatible developmental pathways in retinoblastoma genesis. Cancer cell, 20(2), 260–275. https://doi.org/10.1016/j.ccr.2011.07.005
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
21840489
Department(s)
Administration and Leadership
Document Type
Article