Haematopoietic progenitor cells (HPC) are attracted by experimental
gliomas in vivo. This attraction is further enhanced by irradiation or hypoxic preconditioning of the
glioma cells. Adhesive interactions might be critical to the preferential accumulation of HPC within the
glioma tissue. Here, we studied the interactions of HPC with endothelial cells. Exposure of human cerebral endothelial cells (SV-
HCEC), human microvascular endothelial cells (HMEC) and brain tumour endothelial cells derived from human
glioblastomas (BTEC) to supernatants of
glioma cells and primary
glioma cells (SN-G) induced the expression of
E-selectin (CD62E). CD62E expression was further enhanced when the
glioma cells had been exposed to irradiation or
hypoxia prior to the collection of supernatants, as well as by irradiation or exposure to
hypoxia of the endothelial cells.
Vascular cell adhesion molecule 1 (VCAM-1) was constitutively expressed on SV-
HCEC, HMEC and BTEC, but was not modulated by SN-G, irradiation or
hypoxia. Transendothelial HPC migration was enhanced after CD62E induction in vitro.
Neutralizing antibodies to CD62E strongly reduced the homing of lin(-)Sca-1(+)c-kit(+) cells to orthotopic SMA-560
gliomas in vivo. Tissue microarray sampling normal brain tissue and
astrocytomas of WHO grades II-IV revealed a selective expression of CD62E on endothelial cells of tumour vessels. SN-G-induced CD62E expression on endothelial cells in vitro required
transforming growth factor (
TGF)-beta signalling in
glioma cells and
vascular endothelial growth factor (
VEGF)/
VEGF receptor 2 (VEGF-R2) signalling in endothelial cells. Further, we observed a
nuclear factor kappa B-dependent activation of the CD62E promoter peaking at 12 h after VEGF-R2 activation by
glioma-derived
VEGF. Taken together, we identify
glioma cell-induced CD62E expression on endothelial cells as one mediator of the
glioma tropism of HPC.