Neuronal differentiation and synaptogenesis in retinoblastoma

Dianna A. Johnson, Jiakun Zhang, Sharon Frase, Matthew Wilson, Carlos Rodriguez-Galindo, Michael A. Dyer

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Retinoblastomas initiate in the developing retina in utero and are diagnosed during the first few years of life. We have recently generated a series of knockout mouse models of retinoblastoma that recapitulate the timing, location, and progression of human retinoblastoma. One of the most important benefits of these preclinical models is that we can study the earliest stages of tumor initiation and expansion. This is not possible in human retinoblastoma because tumors initiate in utero and are not diagnosed until they are at an advanced stage. We found that mouse retinoblastoma cells exhibit a surprising degree of differentiation, which has not been previously reported for any neural tumor. Early-stage mouse retinoblastoma cells express proteins found normally in retinal plexiform layers. They also extend neurites and form synapses. All of these features, which were characterized by immunostaining, Golgi-Cox staining, scanning electron microscopy, and transmission electron microscopy, suggest that mouse retinoblastoma cells resemble amacrine/horizontal cells from the retina. As late-stage retinoblastoma cells expand and invade the surrounding tissue, they lose their differentiated morphology and become indistinguishable from human retinoblastomas. Taken together, our data suggest that neuronal differentiation is a hallmark of early-stage retinoblastoma and is lost as cells become more aggressive and invasive. We also show that rosette formation is not a hallmark of retinoblastoma differentiation, as previously believed. Instead, rosette formation reflects extensive cell-cell contacts between retinoblastoma cells in both early-stage (differentiated) and late-stage (dedifferentiated) tumors.

Original languageEnglish (US)
Pages (from-to)2701-2711
Number of pages11
JournalCancer Research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007

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Retinoblastoma
Rosette Formation
Retina
Neoplasms
Amacrine Cells
Neurites
Transmission Electron Microscopy
Knockout Mice
Electron Scanning Microscopy
Synapses

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Johnson, D. A., Zhang, J., Frase, S., Wilson, M., Rodriguez-Galindo, C., & Dyer, M. A. (2007). Neuronal differentiation and synaptogenesis in retinoblastoma. Cancer Research, 67(6), 2701-2711. https://doi.org/10.1158/0008-5472.CAN-06-3754

Neuronal differentiation and synaptogenesis in retinoblastoma. / Johnson, Dianna A.; Zhang, Jiakun; Frase, Sharon; Wilson, Matthew; Rodriguez-Galindo, Carlos; Dyer, Michael A.

In: Cancer Research, Vol. 67, No. 6, 15.03.2007, p. 2701-2711.

Research output: Contribution to journalArticle

Johnson, DA, Zhang, J, Frase, S, Wilson, M, Rodriguez-Galindo, C & Dyer, MA 2007, 'Neuronal differentiation and synaptogenesis in retinoblastoma', Cancer Research, vol. 67, no. 6, pp. 2701-2711. https://doi.org/10.1158/0008-5472.CAN-06-3754
Johnson DA, Zhang J, Frase S, Wilson M, Rodriguez-Galindo C, Dyer MA. Neuronal differentiation and synaptogenesis in retinoblastoma. Cancer Research. 2007 Mar 15;67(6):2701-2711. https://doi.org/10.1158/0008-5472.CAN-06-3754
Johnson, Dianna A. ; Zhang, Jiakun ; Frase, Sharon ; Wilson, Matthew ; Rodriguez-Galindo, Carlos ; Dyer, Michael A. / Neuronal differentiation and synaptogenesis in retinoblastoma. In: Cancer Research. 2007 ; Vol. 67, No. 6. pp. 2701-2711.
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