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LGR5 promotes tumor...
LGR5 promotes tumorigenicity and invasion of glioblastoma stem-like cells and is a potential therapeutic target for a subset of glioblastoma patients
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- Xie, Yuan (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Uppsala universitet, Science for Life Laboratory, SciLifeLab
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- Sundström, Anders (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Neuroonkologi
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- Maturi, Naga P (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Neuroonkologi
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- Tan, E-Jean, 1979- (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Neuroonkologi
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- Marinescu, Voichita D (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala universitet, Institutionen för immunologi, genetik och patologi
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- Jarvius, Malin (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Cancerfarmakologi och beräkningsmedicin
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- Tirfing, Malin (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Uppsala universitet, Science for Life Laboratory, SciLifeLab
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- Jin, Chuan, 1986- (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Klinisk immunologi
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- Chen, Lei, 1985- (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Molekylära verktyg
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- Essand, Magnus (author)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Klinisk immunologi
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- Johansson, Fredrik J., 1975- (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Uppsala universitet, Neuroonkologi
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- Nelander, Sven (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Uppsala universitet, Science for Life Laboratory, SciLifeLab
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- Jiang, Yiwen (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm, Sweden,Uppsala universitet, Science for Life Laboratory, SciLifeLab
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- Uhrbom, Lene (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Uppsala universitet, Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2019-01-10
- 2019
- English.
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In: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 247:2, s. 228-240
- Related links:
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Abstract
Subject headings
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- Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor which lacks efficient treatment and predictive biomarkers. Expression of the epithelial stem cell marker Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been described in GBM, but its functional role has not been conclusively elucidated. Here, we have investigated the role of LGR5 in a large repository of patient-derived GBM stem cell (GSC) cultures. The consequences of LGR5 overexpression or depletion have been analyzed using in vitro and in vivo methods, which showed that, among those with highest LGR5 expression (LGR5(high)), there were two phenotypically distinct groups: one that was dependent on LGR5 for its malignant properties and another that was unaffected by changes in LGR5 expression. The LGR5-responding cultures could be identified by their significantly higher self-renewal capacity as measured by extreme limiting dilution assay (ELDA), and these LGR5(high)-ELDA(high) cultures were also significantly more malignant and invasive compared to the LGR5(high)-ELDA(low) cultures. This showed that LGR5 expression alone would not be a strict marker of LGR5 responsiveness. In a search for additional biomarkers, we identified LPAR4, CCND2, and OLIG2 that were significantly upregulated in LGR5-responsive GSC cultures, and we found that OLIG2 together with LGR5 were predictive of GSC radiation and drug response. Overall, we show that LGR5 regulates the malignant phenotype in a subset of patient-derived GSC cultures, which supports its potential as a predictive GBM biomarker. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- glioblastoma stem-like cells
- LGR5
- self-renewal
- invasion
- radiation response
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Xie, Yuan
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Sundström, Ander ...
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Maturi, Naga P
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Tan, E-Jean, 197 ...
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Marinescu, Voich ...
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Jarvius, Malin
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Tirfing, Malin
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Jin, Chuan, 1986 ...
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Chen, Lei, 1985-
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Essand, Magnus
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Johansson, Fredr ...
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Nelander, Sven
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Jiang, Yiwen
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Uhrbom, Lene
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Journal of Patho ...
- By the university
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Uppsala University
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Karolinska Institutet
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The Swedish School of Sport and Health Sciences