Enhanced expression of Pentraxin-3 in glioblastoma cells correlates with increased invasion and IL8-VEGF signaling axis

In this study, we examined the role of PTX3 in GB growth, angiogenesis, and invasion using in vitro and in vivo GB models, proteomic profiling, molecular and biochemical approaches. Under in vitro conditions, PTX3 over-expression in U87 cells correlated with cell cycle progression, increased migratory potential, and proliferation under hypoxic conditions. Conditioned media containing PTX3 enhanced the angiogenic potential of endothelial cells. While silencing of PTX3 by siRNA decreased the proliferation, migration, and angiogenic potential of U87 cells in vitro. Importantly, PTX3 over-expression increased tumor growth, angiogenesis, and invasion in an orthotopic mouse model. Higher levels of PTX3 in these tumors were associated with the upregulation of inflammatory and angiogenic markers including interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), but decreased levels of thrombospondin-1, an anti-angiogenic factor. Mechanistically, exogenous production of PTX3 triggered an IKK/NFκB signaling pathway that enhances the expression of the motility genes AHGEF7 and Rac1. Taken together, PTX3 expression is dysregulated in GB. PTX3 may augment invasion through enhanced angiogenesis in the GB microenvironment through the IL8-VEGF axis. Thus, PTX3 may represent a potential therapeutic target to mitigate the aggressive behavior of gliomas.PMID:34906547 | DOI:10.1016/j.brainres.2021.147752
Source: Brain Research - Category: Neurology Authors: Source Type: research