Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 14;40(8):240.
doi: 10.1007/s12032-023-02115-5.

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

Bo-Tao Sang  1   2 , Chang-Dong Wang  1   3 , Xing Liu  4 , Jia-Qi Guo  1   2 , Jia-Yi Lai  1   3 , Xiang-Mei Wu  5   6
Affiliations

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

Bo-Tao Sang et al. Med Oncol. .

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.

PubMed Disclaimer

References

    1. Nakata K, Colombet M, Stiller CA, Pritchard-Jones K, Steliarova-Foucher E. Incidence of childhood renal tumours: an international population-based study. Int J Cancer. 2020;147(12):3313–27. - PubMed - PMC
    1. Spreafico F, Fernandez CV, Brok J, Nakata K, Vujanic G, Geller JI, Gessler M, Maschietto M, Behjati S, Polanco A, Paintsil V, Luna-Fineman S, Pritchard-Jones K. Wilms tumour. Nat Rev Dis Primers. 2021;7(1):75. - PubMed
    1. Brok J, Treger TD, Gooskens SL, van den Heuvel-Eibrink MM, Pritchard-Jones K. Biology and treatment of renal tumours in childhood. Eur J Cancer (Oxford). 2016;68:179–95.
    1. Dome JS, Mullen EA, Dix DB, Gratias EJ, Ehrlich PF, Daw NC, Geller JI, Chintagumpala M, Khanna G, Kalapurakal JA, Renfro LA, Perlman EJ, Grundy PE, Fernandez CV. Impact of the first generation of Children’s Oncology Group Clinical trials on clinical practice for Wilms tumor. J Natl Compr Cancer Netw. 2021;19(8):978–85.
    1. Mullen EA, Chi Y-Y, Hibbitts E, Anderson JR, Steacy KJ, Geller JI, Green DM, Khanna G, Malogolowkin MH, Grundy PE, Fernandez CV, Dome JS. Impact of surveillance imaging modality on survival after recurrence in patients with favorable-histology wilms tumor: a report from the Children’s Oncology Group. J Clin Oncol. 2018;36:3396. - PMC

MeSH terms

Substances

LinkOut - more resources