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Prominin 1/CD133 endothelium sustains growth of proneural glioma.

TitleProminin 1/CD133 endothelium sustains growth of proneural glioma.
Publication TypeJournal Article
Year of Publication2013
AuthorsDing B-S, James D, Iyer, iv R, Falciatori I, Hambardzumyan D, Wang S, Butler JM, Rabbany SY, Hormigo A
JournalPLoS One
Volume8
Issue4
Paginatione62150
Date Published2013
ISSN1932-6203
KeywordsAnimals, Antigens, CD, Astrocytes, Brain, Cell Proliferation, Endothelium, Gene Expression Regulation, Neoplastic, Glioblastoma, Glycoproteins, Mice, Mice, Inbred C57BL, Neoplastic Stem Cells, Neurogenesis, Neurons, Peptides, Phenotype
Abstract

In glioblastoma high expression of the CD133 gene, also called Prominin1, is associated with poor prognosis. The PDGF-driven proneural group represents a subset of glioblastoma in which CD133 is not overexpressed. Interestingly, this particular subset shows a relatively good prognosis. As with many other tumors, gliobastoma is believed to arise and be maintained by a restricted population of stem-like cancer cells that express the CD133 transmembrane protein. The significance of CD133(+) cells for gliomagenesis is controversial because of conflicting supporting evidence. Contributing to this inconsistency is the fact that the isolation of CD133(+) cells has largely relied on the use of antibodies against ill-defined glycosylated epitopes of CD133. To overcome this problem, we used a knock-in lacZ reporter mouse, Prom1(lacZ/+) , to track Prom1(+) cells in the brain. We found that Prom1 (prominin1, murine CD133 homologue) is expressed by cells that express markers characteristic of the neuronal, glial or vascular lineages. In proneural tumors derived from injection of RCAS-PDGF into the brains of tv-a;Ink4a-Arf(-/-) Prom1(lacZ/+) mice, Prom1(+) cells expressed markers for astrocytes or endothelial cells. Mice co-transplanted with proneural tumor sphere cells and Prom1(+) endothelium had a significantly increased tumor burden and more vascular proliferation (angiogenesis) than those co-transplanted with Prom1(-) endothelium. We also identified specific genes in Prom1(+) endothelium that code for endothelial signaling modulators that were not overexpressed in Prom1(-) endothelium. These factors may support proneural tumor progression and could be potential targets for anti-angiogenic therapy.

DOI10.1371/journal.pone.0062150
Alternate JournalPLoS ONE
PubMed ID23637986
PubMed Central IDPMC3636202