Bone Marrow-Derived Mesenchymal Stem Cells Differentially Affect Glioblastoma Cell Proliferation, Migration, and Invasion: A 2D-DIGE Proteomic Analysis

Biomed Res Int. 2021 Feb 11:2021:4952876. doi: 10.1155/2021/4952876. eCollection 2021.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) display high tumor tropism and cause indirect effects through the cytokines they secrete. However, the effects of BM-MSCs on the biological behaviors of glioblastoma multiforme remain unclear. In this study, the conditioned medium from BM-MSCs significantly inhibited the proliferation of C6 cells (P < 0.05) but promoted their migration and invasion (P < 0.05). Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) proteomic analysis revealed 17 proteins differentially expressed in C6 cells exposed to the BM-MSC-conditioned medium including five upregulated proteins and 12 downregulated proteins. Among these, six differentially expressed proteins (Calr, Set, Oat, Npm1, Ddah1, and Tardbp) were closely related to cell proliferation and differentiation, and nine proteins (Pdia6, Sphk1, Anxa4, Vim, Tuba1c, Actr1b, Actn4, Rap2c, and Tpm2) were associated with motility and the cytoskeleton, which may modulate the invasion and migration of tumor cells. Above all, by identifying the differentially expressed proteins using proteomics and bioinformatics analysis, BM-MSCs could be genetically modified to specifically express tumor-suppressive factors when BM-MSCs are to be used as tumor-selective targeting carriers in the future.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Movement* / physiology
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / physiology
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Cytokines / metabolism
  • Female
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Nude
  • Nucleophosmin
  • Proteome / analysis*
  • Proteome / drug effects
  • Proteome / metabolism
  • Proteomics / methods
  • Rats
  • Rats, Sprague-Dawley
  • Two-Dimensional Difference Gel Electrophoresis / methods

Substances

  • Culture Media, Conditioned
  • Cytokines
  • Npm1 protein, mouse
  • Proteome
  • Nucleophosmin