Neuropathological and genomic characterization of glioblastoma-induced rat model: How similar is it to humans for targeted therapy?

J Cell Physiol. 2019 Dec;234(12):22493-22504. doi: 10.1002/jcp.28813. Epub 2019 May 23.

Abstract

Glioblastoma multiforme (GBM) is a unique aggressive tumor and mostly develops in the brain, while rarely spreading out of the central nervous system. It is associated with a high mortality rate; despite tremendous efforts having been made for effective therapy, tumor recurrence occurs with high prevalence. To elucidate the mechanisms that lead to new drug discovery, animal models of tumor progression is one of the oldest and most beneficial approaches to not only investigating the aggressive nature of the tumor, but also improving preclinical research. It is also a useful tool for predicting novel therapies' effectiveness as well as side effects. However, there are concerns that must be considered, such as the heterogeneity of tumor, biological properties, pharma dynamic, and anatomic shapes of the models, which have to be similar to humans as much as possible. Although several methods and various species have been used for this approach, the real recapitulation of the human tumor has been left under discussion. The GBM model, which has been verified in this study, has been established by using the Rat C6 cell line. By exploiting bioinformatic tools, the similarities between aberrant gene expression and pathways have been predicted. In this regard, 610 common genes and a number of pathways have been detected. Moreover, while magnetic resonance imaging analysis enables us to compare tumor features between these two specious, pathological findings provides most of the human GBM characteristics. Therefore, the present study provides genomics, pathologic, and imaging evidence for showing the similarities between human and rat GBM models.

Keywords: drug target therapy; gene expression; glioblastoma multiforme; protein−protein interaction; rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Computational Biology
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genomics*
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Neoplasms, Experimental
  • Protein Interaction Maps
  • Rats
  • Species Specificity
  • Transcriptome
  • Up-Regulation