Analysis of the RNA-Seq data from The Cancer Genome Atlas database showed that the increased SPP1 mRNA expression in lower-grade glioma was significantly associated with poor survival outcomes in patients with lower-grade glioma.
We reveal that SPP1 is overexpressed in glioma initiating cells defined by high rhodamine 123 efflux, sphere forming capacity and stemness marker expression.
We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells.
These strategies allow us to define an important role of OPN in conferring cancer hallmarks, which can be further applied to assess the functional roles of other candidate genes in glioma.
To elucidate the role of OPN in the process of glioma angiogenesis, endothelial progenitor cells (EPCs) were treated with conditioned media of human glioma SHG44 cells overexpressing OPN.
Both OPN-a Mu and -c Mu promoted glioma cell invasion through alteration of the levels of uPA, MMP-2, and MMP-9 expressions and the activities of MMP-2 and MMP-9 via activation PI-3K/AKT/NF-kappaB signaling pathway.
This is the first demonstration that OPN inhibition blocks glioma tumor growth, making this invasion-related protein an attractive target for glioma therapy.