Inhibition of carcinoma cell growth and metastasis by a vesicular stomatitis virus G-pseudotyped retrovector expressing type I insulin-like growth factor receptor antisense

Hum Gene Ther. 2001 Nov 1;12(16):1969-77. doi: 10.1089/104303401753204544.


A replication-defective, vesicular stomatitis virus G-pseudotyped, Moloney murine leukemia virus retroviral vector (vLTR-IGF-IR(AS)) was generated in which a type I insulin-like growth factor receptor (IGF-IR) antisense fragment is expressed in a bicistronic mRNA with an enhanced green fluorescent protein (EGFP) reporter under the control of a potent long terminal repeat (LTR). The suitability of these retroparticles for gene therapy was tested with highly metastatic, carcinoma H-59 cells, which depend on IGF-IR expression for tumorigenicity and metastasis. Transduction with these, but not with control retroviral particles expressing EGFP only, resulted in a 70% reduction in IGF-IR levels and the loss of IGF-IR-regulated functions. Moreover, the ability of vLTR-IGF-IR(AS) retroparticle-transduced tumor cells to form experimental hepatic metastases was significantly reduced relative to controls. The results identify retrovector-mediated delivery of IGF-IR antisense as a potential strategy for cancer gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / genetics*
  • Carcinoma, Lewis Lung / pathology
  • Cell Division / genetics*
  • Female
  • Genetic Vectors*
  • Green Fluorescent Proteins
  • Luminescent Proteins / genetics
  • Membrane Glycoproteins*
  • Mice
  • Neoplasm Metastasis / prevention & control*
  • Oligonucleotides, Antisense / genetics*
  • Receptor, IGF Type 1 / genetics*
  • Transduction, Genetic
  • Tumor Cells, Cultured
  • Viral Envelope Proteins / genetics*


  • G protein, vesicular stomatitis virus
  • Luminescent Proteins
  • Membrane Glycoproteins
  • Oligonucleotides, Antisense
  • Viral Envelope Proteins
  • Green Fluorescent Proteins
  • Receptor, IGF Type 1