CXCR4 antagonists as stem cell mobilizers and therapy sensitizers for acute myeloid leukemia and glioblastoma?

Vashendriya V. V. Hira (Author), Cornelis J. F. van Noorden (Author), Remco J. Molenaar (Author)

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.

Keywords

glioblastoma;matične celice;akutna mielonična levkemija;kostni mozeg;glioblastoma stem cells;niches;acute myeloid leukemia;hematopoietic stem cells;bone marrow;C-X-C receptor type 4;stromal-derived factor-1 ▫$[alpha]$▫;plerixafor;

Data

Language:	English
Year of publishing:	2020
Typology:	1.03 - Short Scientific Article
Organization:	NIB - National Institute of Biology
UDC:	577
COBISS:	40521221
ISSN:	2079-7737
Views:	43
Downloads:	11
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	glioblastoma;matične celice;glioblastoma;akutna mielonična levkemija;kostni mozeg;
Source comment:	Nasl. z nasl. zaslona; Opis vira z dne 30. 3. 2020;
Pages:	str. 1-10
Volume:	ǂVol. ǂ9
Issue:	ǂiss. ǂ31
Chronology:	17 Feb. 2020
DOI:	10.3390/biology9020031
ID:	24670032