Document Detail


Tumor-associated retinal astrocytes promote retinoblastoma cell proliferation through production of IGFBP-5.
MedLine Citation:
PMID:  20508032     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinoblastomas consist of cone-like neoplastic cells and diverse non-neoplastic cells whose roles in tumorigenesis have not been defined. Here, we investigated the glial cells that constitute 2% to 3% of the cells in retinoblastoma tumors, including their origin, their relationship to a potential retinoblastoma stem cell population, and their effects on tumor cell proliferation. Retinoblastoma glia consistently expressed the retinal astrocyte marker Pax2 but inconsistently expressed the Müller cell and occasional astrocyte marker CRALBP. Many of the glia expressed the stem cell-associated Sox2 but nevertheless were non-neoplastic as they coexpressed Rb and/or retained two RB1 alleles. Conversely, the glia were distinct from the non-neoplastic cells that strongly expressed the stem cell-associated ABCG2. Adherent Pax2(+),Sox2(+),Rb(+) glia readily grew from explanted retinoblastomas and produced soluble factors that enhanced the proliferation of cocultured retinoblastoma cells. This effect was emulated by normal retinal glia and appeared to be mediated by insulin-like growth factor binding protein-5 (IGFBP-5), as it was mimicked by recombinant IGFBP-5 and mitigated by neutralizing IGFBP-5 antibody. As glia-derived IGFBP-5 was earlier found to promote photoreceptor survival, our findings indicate that retinal astrocytes enhance the proliferation of cone-like retinoblastoma cells by deploying a factor that also provides trophic support to the tumor cells' non-neoplastic counterparts. These observations suggest that a tissue-specific microenvironmental feature cooperates with oncogenic mutations in a cancer cell of origin to promote retinoblastoma tumorigenesis.
Authors:
Xiaoliang L Xu; Thomas C Lee; Nneka Offor; Christine Cheng; Aihong Liu; Yuqiang Fang; Suresh C Jhanwar; David H Abramson; David Cobrinik
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-27
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-07     Completed Date:  2010-12-06     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424-35     Citation Subset:  AIM; IM    
Affiliation:
Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / metabolism*,  pathology
Biological Markers / metabolism
Cell Line
Cell Proliferation*
Cell Survival
Coculture Techniques
Humans
Insulin-Like Growth Factor Binding Protein 5 / metabolism*
Mice
Retinal Neoplasms* / metabolism,  pathology
Retinoblastoma* / metabolism,  pathology
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Insulin-Like Growth Factor Binding Protein 5
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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