Characterization of human mesothelioma cell lines as tumor models for suicide gene therapy

Onkologie. 2008 Mar;31(3):91-6. doi: 10.1159/000113504. Epub 2008 Feb 8.

Abstract

Background: The median survival time of patients with malignant pleural mesothelioma (MPM) remains poor. Therefore, novel therapeutic options are in high demand, and well characterized model systems for in vitro/vivo screening have to be established.

Material and methods: For this purpose, 3 MPM cell lines (H-Meso-1, MSTO211H, and NCI-H28) were characterized and tested for susceptibility to recombinant adeno-associated virus 2 (rAAV2)-based vectors which have the potential for a loco-regional application.

Results: Using multiplex fluorescence in situ hybridization, several recurrent chromosomal aberrations were observed for each of the MPM cell lines. Tumorigenicity of H-Meso-1 and MSTO-211H cells was shown in an intraperitoneal NOD/SCID mouse model, whereas NCI-H28 cells did not yield any tumors. Although all 3 cell lines were readily susceptible to rAAV2 vectors, differences in susceptibility were observed (H-Meso-1 > NCI-H28 > MSTO-211H). Furthermore, the efficacy of a potential suicide gene therapy using an rAAV2 suicide vector-transduced MPM cell line was determined in a proof-of-feasibility in vivo experiment.

Conclusion: The characterized cell lines described here may serve as a model for in vitro and in vivo preclinical gene therapy for the treatment of MPM using rAAV2 suicide vectors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Genes, Transgenic, Suicide / genetics*
  • Genetic Therapy / methods*
  • Mesothelioma / genetics*
  • Mesothelioma / therapy*
  • Mice
  • Mice, SCID
  • Transduction, Genetic / methods*