TY - JOUR
T1 - CD133+ and Nestin+ Glioma Stem-Like Cells Reside Around CD31+ Arterioles in Niches that Express SDF-1α, CXCR4, Osteopontin and Cathepsin K
AU - Hira, V.V.V.
AU - Ploegmakers, K.J.
AU - Grevers, F.
AU - Verbovšek, U.
AU - Silvestre-Roig, C.
AU - Aronica, E.
AU - Tigchelaar, W.
AU - Turnšek, T.L.
AU - Molenaar, R.J.
AU - van Noorden, C.J.F.
N1 - With supplemental figures
PY - 2015/7
Y1 - 2015/7
N2 - Poor survival of high-grade glioma is at least partly caused by glioma stem-like cells (GSLCs) that are resistant to therapy. GSLCs reside in niches in close vicinity of endothelium. The aim of the present study was to characterize proteins that may be functional in the GSLC niche by performing immunohistochemistry on serial cryostat sections of human high-grade glioma samples. We have found nine niches in five out of five high-grade glioma samples that were all surrounding arterioles with CD31+ endothelial cells and containing cellular structures that were CD133+ and nestin+. All nine niches expressed stromal-derived factor-1alpha (SDF-1alpha), its receptor C-X-C chemokine receptor type 4 (CXCR4), osteopontin and cathepsin K. SDF-1alpha plays a role in homing of CXCR4+ stem cells and leukocytes, whereas osteopontin and cathepsin K promote migration of cancer cells and leukocytes. Leukocyte-related markers, such as CD68, macrophage matrix metalloprotease-9, CD177 and neutrophil elastase were often but not always detected in the niches. We suggest that SDF-1alpha is involved in homing of CXCR4+ GSLCs and leukocytes and that cathepsin K and osteopontin are involved in the migration of GSLCs out of the niches.
AB - Poor survival of high-grade glioma is at least partly caused by glioma stem-like cells (GSLCs) that are resistant to therapy. GSLCs reside in niches in close vicinity of endothelium. The aim of the present study was to characterize proteins that may be functional in the GSLC niche by performing immunohistochemistry on serial cryostat sections of human high-grade glioma samples. We have found nine niches in five out of five high-grade glioma samples that were all surrounding arterioles with CD31+ endothelial cells and containing cellular structures that were CD133+ and nestin+. All nine niches expressed stromal-derived factor-1alpha (SDF-1alpha), its receptor C-X-C chemokine receptor type 4 (CXCR4), osteopontin and cathepsin K. SDF-1alpha plays a role in homing of CXCR4+ stem cells and leukocytes, whereas osteopontin and cathepsin K promote migration of cancer cells and leukocytes. Leukocyte-related markers, such as CD68, macrophage matrix metalloprotease-9, CD177 and neutrophil elastase were often but not always detected in the niches. We suggest that SDF-1alpha is involved in homing of CXCR4+ GSLCs and leukocytes and that cathepsin K and osteopontin are involved in the migration of GSLCs out of the niches.
UR - https://pure.uva.nl/ws/files/2666434/169726_CD133_and_Nestin_Glioma_Stem_Like_Cells_suppl.pdf
U2 - https://doi.org/10.1369/0022155415581689
DO - https://doi.org/10.1369/0022155415581689
M3 - Article
C2 - 25809793
SN - 0022-1554
VL - 63
SP - 481
EP - 493
JO - The Journal of Histochemistry and Cytochemistry
JF - The Journal of Histochemistry and Cytochemistry
IS - 7
ER -