Inhibition of carcinoma cell growth and metastasis by a vesicular stomatitis virus G-pseudotyped retrovector expressing type I insulin-like growth factor receptor antisense.
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.
Samani
A A
AA
Department of Medicine, McGill University Health Center-Royal Victoria Hospital, Montreal, Quebec, Canada.
Fallavollita
L
L
Jaalouk
D E
DE
Galipeau
J
J
Brodt
P
P
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000235:genetics*
C028391:G protein, vesicular stomatitis virus; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D014759:Viral Envelope Proteins; D049452:Green Fluorescent Proteins; D017526:Receptor, IGF Type 1