PDGF-BB/PDGFRβ induces tumour angiogenesis via enhancing PKM2 mediated by the PI3K/AKT pathway in Wilms' tumour

Abstract

Platelet-derived growth factor receptor-β (PDGFRβ) is a critical type III receptor tyrosine kinase family member, which is involved in Wilms' tumour (WT) metastasis and aerobic glycolysis. The role of PDGFRβ in tumour angiogenesis has not been fully elucidated. Here, we examined the effect of PDGFRβ on angiogenesis in WT. First, the NCBI database integrated three datasets, GSE2712, GSE11151, and GSE73209, to screen differentially expressed genes. The R language was used to analyse the correlation between PDGFRB and vascular endothelial growth factor (VEGF). The results showed that PDGFRB, encoding PDGFRβ, was upregulated in WT, and its level was correlated with VEGFA expression. Next, PDGFRβ expression was inhibited by small interfering RNA (siRNA) or activated with the exogenous ligand PDGF-BB. The expression and secretion of the angiogenesis elated factor VEGFA in WT G401 cells were detected using Western blotting and ELISA, respectively. The effects of conditioned medium from G401 cells on endothelial cell viability, migration, invasion, the total length of the tube, and the number of fulcrums were investigated. To further explore the mechanism of PDGFRβ in the angiogenesis of WT, the expression of VEGFA was detected after blocking the phosphatidylinositol-3-kinase (PI3K) pathway and inhibiting the expression of PKM2, a key enzyme of glycolysis. The results indicated that PDGFRβ regulated the process of tumour angiogenesis through the PI3K/AKT/PKM2 pathway. Therefore, this study provides a novel therapeutic strategy to target PDGFRβ and PKM2 to inhibit glycolysis and anti-angiogenesis, thus, developing a new anti-vascular therapy.

Keywords: Anti-vascular therapy; Endothelial cells; PDGFRβ; PKM2; VEGFA; Wilms’ tumour.