title: Prominin 1/CD133 endothelium sustains growth of proneural glioma.
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.
authors: Ansary Stem Cell Institute, and Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors: Bi-Sen
authors: BS
authors: Ding
authors: Daylon
authors: D
authors: James
authors: Rajiv
authors: R
authors: Iyer
authors: Ilaria
authors: I
authors: Falciatori
authors: Dolores
authors: D
authors: Hambardzumyan
authors: Su
authors: S
authors: Wang
authors: Jason M
authors: JM
authors: Butler
authors: Sina Y
authors: SY
authors: Rabbany
authors: Adília
authors: A
authors: Hormigo
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006023:Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000172:deficiency / Q000378:metabolism*; D010641:Phenotype
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse
references: FEBS Lett. 2007 May 1;581(9):1783-7
references: 17428477
references: Traffic. 2001 Feb;2(2):82-91
references: 11247306
references: Blood. 2004 Mar 15;103(6):2055-61
references: 14630820
references: Cancer Cell. 2010 Jan 19;17(1):98-110
references: 20129251
references: Tissue Antigens. 2007 Jun;69(6):602-6
references: 17498271
references: Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4271-2
references: 21383166
references: Blood. 1997 Dec 15;90(12):5002-12
references: 9389720
references: Nature. 2008 Apr 10;452(7188):759-63
references: 18401410
references: Cell Stem Cell. 2008 Sep 11;3(3):265-78
references: 18786414
references: Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4274-80
references: 21262804
references: Cell Stem Cell. 2008 Sep 11;3(3):279-88
references: 18786415
references: Cancer Cell. 2009 Mar 3;15(3):232-9
references: 19249681
references: Cell Stem Cell. 2010 Feb 5;6(2):141-52
references: 20144787
references: Science. 1994 May 20;264(5162):1145-8
references: 8178174
references: Clin Cancer Res. 2005 Aug 1;11(15):5390-5
references: 16061852
references: Nat Neurosci. 2006 Mar;9(3):331-9
references: 16491078
references: J Neurosci. 2009 Feb 18;29(7):2297-308
references: 19228982
references: PLoS One. 2010 Jun 01;5(6):e10917
references: 20532232
references: Neoplasia. 2005 Apr;7(4):356-68
references: 15967113
references: PLoS One. 2011;6(7):e20605
references: 21754979
references: Cancer Cell. 2007 Jan;11(1):69-82
references: 17222791
references: J Neurosci. 2006 Jul 26;26(30):7907-18
references: 16870736
references: Nature. 2004 Nov 18;432(7015):396-401
references: 15549107
references: Cancer Cell. 2009 Mar 3;15(3):220-31
references: 19249680
references: PLoS One. 2009 Nov 13;4(11):e7752
references: 19915670
references: Blood. 1997 Dec 15;90(12):5013-21
references: 9389721
references: J Cell Sci. 1999 Apr;112 ( Pt 7):1023-33
references: 10198284
references: Neuron. 1993 Jul;11(1):173-89
references: 8338665
references: Nat Rev Cancer. 2010 Feb;10(2):138-46
references: 20094048
references: Nat Neurosci. 2005 Jun;8(6):723-9
references: 15908947
references: Cell. 1999 Jan 8;96(1):25-34
references: 9989494
references: Cancer Cell. 2006 Mar;9(3):157-73
references: 16530701
references: J Clin Invest. 2008 Jun;118(6):2111-20
references: 18497886
references: Cell. 1999 Jun 11;97(6):703-16
references: 10380923
references: Cancer Res. 2004 Oct 1;64(19):7011-21
references: 15466194
references: Brain. 2010 Apr;133(Pt 4):973-82
references: 20375132
references: Neurosurgery. 2008 Feb;62(2):505-14; discussion 514-5
references: 18382330
references: J Mol Med (Berl). 2008 Sep;86(9):1025-32
references: 18535813
references: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1026-31
references: 18195354
references: Clin Cancer Res. 2008 Apr 15;14(8):2378-86
references: 18413828
references: Ann Neurol. 2006 May;59(5):763-79
references: 16634042
references: Cancer Lett. 2007 Dec 18;258(2):286-90
references: 17977646
references: Cell Stem Cell. 2008 Sep 11;3(3):289-300
references: 18786416