Lipoprotein lipase and phospholipid transfer protein overexpression in human glioma cells and their effect on cell growth, apoptosis, and migration

Acta Biochim Biophys Sin (Shanghai). 2017 Jan;49(1):62-73. doi: 10.1093/abbs/gmw117. Epub 2016 Nov 17.

Abstract

Glioma is one of the common tumors in brain. The expression level of lipoprotein lipase (LPL) or phospholipid transfer protein (PLTP) may influence glioma progression and its relationship with clinical and pathological parameters. The clinical significance of LPL or PLTP expression in glioma has not been established. In the present study, the LPL and PLTP levels in glioma tumors were investigated and the relationship between the LPL and PLTP level and the grade of malignant glioma was analyzed, with the aim to provide new ideas for the diagnosis and treatment of gliomas in clinical and basic research settings. LPL and PLTP mRNA and protein levels were significantly higher in Grade IV glioma than those in the lower grade tumors (P < 0.01). Double immunofluorescent staining showed that the levels of LPL and PLTP were significantly associated with the pathological grade of glioma (P = 0.005). The levels of LPL and PLTP were increased with the shortened survival of glioma patients (P < 0.001). Knockdown of LPL and PLTP led to decreased cell growth and migration but increased apoptosis in vitro Additionally, cell cycle-related cyclins and their partners were found to be down-regulated while cyclin-dependent kinase inhibitors p16, p21, and Rb were up-regulated. Furthermore, knockdown of LPL or PLTP resulted in the up-regulation of pro-apoptotic molecules and the down-regulation of anti-apoptotic molecules. Ablation of LPL or PLTP in U251 cells resulted in the down-regulation of epithelial mesenchymal transition markers and invasion molecules matrix metalloproteinases. LPL and PLTP appear to be novel glioma-associated proteins and play a role in the progression of human glioma.

Keywords: LPL; PLTP; apoptosis; colony formation; glioma; migration.

MeSH terms

  • Apoptosis*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Division*
  • Cell Line, Tumor
  • Cell Movement*
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism*
  • Phospholipid Transfer Proteins / genetics
  • Phospholipid Transfer Proteins / metabolism*
  • RNA, Small Interfering / genetics

Substances

  • Phospholipid Transfer Proteins
  • RNA, Small Interfering
  • Lipoprotein Lipase