In the present study, we designed and synthesized <sup>99<i>m</i></sup>Tc-labeled low-generation dendrimer-entrapped gold nanoparticles (Au DENPs), which were modified with CXCR4-ligand for targeted single photon emission computed tomography (SPECT)/computed tomography (CT) imaging of glioma.
The effects of NT21MP on CXCR4 expression, cell survival and migration were assessed on the human glioma cell line U251 and SHG-44 exposed to SDF-1α, by western blotting, MTT assay, flow cytometry and transwell migration assay.
Additionally, genetic down regulation of CXCR4 in mouse glioma GL26-Cit cells inhibits their in-vitro migration towards MBVE cells; in an in-vivo intracranial mouse model, these cells display reduced tumor growth and perivascular invasion, leading to increased survival.
In order to illustrate the effect of CXCR4 on glioma metastasis, we investigated the role of CXCR4 in U87 cells metastasis based on the CXCR4 silencing tumor cells.
Not only is the expression of CXCR4 a key determinant of glioma progression, but SDF-1α is essential for site-specific invasive or metastatic processes.
As such, this article presents such a framework with regard to the CXCR4 pathway in glioma thereby supporting the further investigation of CXCR4 as a therapeutic target in patients with this disease.
We thus demonstrate the utility of GSf lines in testing therapeutic agents and validate CXCR4 as a target to block the growth of invasive tumor-initiating glioma stem cells in vivo.
These results indicate that SDF-1α/CXCR4 could be involved in recruitment of hUCB-MSCs to glioma cells and that overexpression of CXCR4 may be a useful tool for stem cell-based glioma therapy.
In human glioma specimens the levels of CXCL11 and CXCR4 mRNA were significantly higher in glioblastomas compared to non-tumor controls or low grade gliomas, whilst no difference was found for CXCL12 and CXCR7 mRNA expression.
Flow cytometry was used to determine transduction efficiencies in NP2/CD4/CXCR4 (glioma cell line stably transduced with the HIV receptors) and HeLa/CD4 cell lines.
We report here with the basis of microarray gene expression analysis that CXCR4 expressing glioma cells are capable of expressing PAI-1 mRNA and protein upon CXCL12 stimulation.
Significantly, when patients with glioblastoma multiforme were segregated into two groups based on CXCR4 expression level, we observed a statistically significant increase in the intensity and extent of peritumoral magnetic resonance imaging signal abnormalities associated with CXCR4 high-expressing gliomas.
These observations indicate that hypoxia is a key factor in determining NSC tropism to glioma and that SDF-1/CXCR4, uPA/uPAR, VEGF/VEGFR2, and hepatocyte growth factor/c-Met signaling pathways mediate increased NSC-to-glioma tropism under hypoxia.