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| Status |
Public on Mar 05, 2020 |
| Title |
Expression data from ABCB5-positive and ABCB5-negative GBM cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We analyzed, by HTA 2.0, the GBM cell lines LN-18, LN-229, and U-87 MG after fluoresence-activated cell sorting (FACS) into ABCB5+ and ABCB5- fractions. Poor prognosis associated with glioblastoma multiforme (GBM) results from tumor resistance to therapy and high rate of recurrence. Compelling evidence suggests this is driven by subpopulations of slow-proliferating cancer stem cells with tumor-initiating potential. ATP-binding cassette member B5 (ABCB5) has been identified as a molecular marker for distinct subsets of chemoresistant tumor-initiating cell populations in diverse human malignancies. In the current study, we examined the potential role of ABCB5 in growth and chemoresistance of GBM. We found ABCB5 to be preferentially expressed in clinical GBM tumors and co-expressed with the stem cell marker CD133 in subpopulations of human GBM cell lines U-87 MG, LN-18 and LN-229. Antibody-mediated functional ABCB5 blockade inhibited proliferation and survival of human GBM cells and sensitized them to temozolomide (TMZ)-induced apoptosis. Likewise, in an in vivo GBM xenograft study in immunodeficient mice, anti-ABCB5 monoclonal antibody treatment inhibited tumor growth and sensitized tumors to TMZ therapy. Mechanistically, we demonstrated that ABCB5 regulates cell cycle checkpoint molecules to revoke drug-induced G2-M arrest and augments drug-mediated cell death. Overall, our data establish ABCB5 as a marker of GBM chemoresistance and point to the potential of ABCB5 targeting in improvement of current GBM therapies.
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| Overall design |
Three GBM cell lines were FACS sorted for ABCB5 using anti-ABCB5 mAb clone 3C2-1D12. The sorted populations were collected for RNA extraction and microarray analysis.
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| Contributor(s) |
Lee CA, Frank NY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Mar 05, 2019 |
| Last update date |
Mar 06, 2020 |
| Contact name |
Natasha Frank |
| Organization name |
Brigham and Women's Hospital
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| Department |
Medicine
|
| Lab |
Natasha Frank
|
| Street address |
77 Avenue Louis Pasteur
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA525717 |
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