| Title: | CXCR4 antagonists as stem cell mobilizers and therapy sensitizers for acute myeloid leukemia and glioblastoma? |
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| Authors: | ID Hira, Vashendriya V. V. (Author)
ID Noorden, Cornelis J. F. van (Author)
ID Molenaar, Remco J. (Author) |
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| Files: |  URL - Source URL, visit https://www.mdpi.com/2079-7737/9/2/31
 PDF - Presentation file, download (1,51 MB)
MD5: 141860D0097387337E12B9B19A571323
URL - Source URL, visit https://doi.org/10.3390/biology9020031
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| Language: | English |
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| Typology: | 1.03 - Other scientific articles |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | Glioblastoma is the most aggressive and malignant primary brain tumor in adults and has a poor patient survival of only 20 months after diagnosis. This poor patient survival is at least partly caused by glioblastoma stem cells (GSCs), which are slowly-dividing and therefore therapy-resistant. GSCs are localized in protective hypoxic peri-arteriolar niches where these aforementioned stemness properties are maintained. We previously showed that hypoxic peri-arteriolar GSC niches in human glioblastoma are functionally similar to hypoxic peri-arteriolar hematopoietic stem cell (HSC) niches in human bone marrow. GSCs and HSCs express the receptor C-X-C receptor type 4 (CXCR4), which binds to the chemoattractant stromal-derived factor-1α (SDF-1α), which is highly expressed in GSC niches in glioblastoma and HSC niches in bone marrow. This receptor–ligand interaction retains the GSCs/HSCs in their niches and thereby maintains their slowly-dividing state. In acute myeloid leukemia (AML), leukemic cells use the SDF-1α–CXCR4 interaction to migrate to HSC niches and become slowly-dividing and therapy-resistant leukemic stem cells (LSCs). In this communication, we aim to elucidate how disruption of the SDF-1α–CXCR4 interaction using the FDA-approved CXCR4 inhibitor plerixafor (AMD3100) may be used to force slowly-dividing cancer stem cells out of their niches in glioblastoma and AML. Ultimately, this strategy aims to induce GSC and LSC differentiation and their sensitization to therapy.
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| Keywords: | glioblastoma, glioblastoma stem cells, niches, acute myeloid leukemia, hematopoietic stem cells, bone marrow, C-X-C receptor type 4, stromal-derived factor-1 ▫$[alpha]$▫, plerixafor |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 12.02.2020 |
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| Year of publishing: | 2020 |
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| Number of pages: | str. 1-10 |
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| Numbering: | Vol. 9, iss. 31 |
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| PID: | 20.500.12556/DiRROS-20163  |
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| UDC: | 577 |
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| ISSN on article: | 2079-7737 |
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| DOI: | 10.3390/biology9020031 |
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| COBISS.SI-ID: | 40521221 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 30. 3. 2020;
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| Publication date in DiRROS: | 06.08.2024 |
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| Views: | 314 |
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| Downloads: | 400 |
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