Retroviral delivery of platelet-derived growth factor to spinal cord progenitor cells drives the formation of intramedullary gliomas

Neurosurgery. 2012 Jan;70(1):198-204; discussion 204. doi: 10.1227/NEU.0b013e31822ce963.

Abstract

Background: High-grade gliomas of the spinal cord are poorly understood tumors that are very commonly associated with bad outcomes. The transforming effects of platelet-derived growth factor (PDGF) on spinal cord glial progenitor cells may play an important role in the development of these tumors.

Objective: To investigate the possible tumor-initiating effects of PDGF overexpression in the spinal cord, we delivered a PDGF retrovirus directly into the substance of the spinal cord.

Methods: The spinal cords of wild-type adult rats were surgically exposed and injected with 10⁶ colony-forming units of a green fluorescent protein-tagged, PDGF-expressing retrovirus. A control virus was injected to assess the cell types that become infected during retroviral delivery to the spinal cord.

Results: It was observed that PDGF overexpression in the spinal cord causes morbidity from high-grade intramedullary glioma formation between 27 and 49 days after PDGF retrovirus injection. Retroviral transduction was highly efficient with 100% of injected animals displaying the tumor phenotype. The tumors produced were highly proliferative, were locally invasive, and displayed the immunophenotype of virus-targeted glial progenitor cells (Olig2+PDGFR+NG2+GFAP-).

Conclusion: PDGF is capable of driving glial progenitor cells within the adult spinal cord to form high-grade gliomas. Further investigation of PDGF signaling in the spinal cord is needed to better understand and treat these devastating tumors.

MeSH terms

  • Animals
  • Antigens / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Glioma / chemically induced*
  • Glioma / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Platelet-Derived Growth Factor / biosynthesis
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / toxicity*
  • Proteoglycans / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Retroviridae / genetics
  • Retroviridae / metabolism
  • Spinal Cord Neoplasms / chemically induced*
  • Spinal Cord Neoplasms / metabolism*
  • Stem Cells / metabolism*
  • Time Factors

Substances

  • Antigens
  • Basic Helix-Loop-Helix Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Olig2 protein, rat
  • Oligodendrocyte Transcription Factor 2
  • Platelet-Derived Growth Factor
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • Green Fluorescent Proteins
  • Receptor, Platelet-Derived Growth Factor alpha
  • Bromodeoxyuridine