Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo

J Neurooncol. 2016 Sep;129(2):201-9. doi: 10.1007/s11060-016-2168-z. Epub 2016 Jun 9.

Abstract

Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas.

Keywords: Gliomas; Invasion; Migration; Pentraxin 3; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Cycle / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Serum Amyloid P-Component / genetics
  • Serum Amyloid P-Component / metabolism*

Substances

  • RNA, Small Interfering
  • Serum Amyloid P-Component
  • PTX3 protein
  • C-Reactive Protein
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1