Characterization of Human Mesothelioma Cell Lines as Tumor Models for Suicide Gene Therapy

Vol. 31, No. 3, 2008

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Original Article · Originalarbeit

Characterization of Human Mesothelioma Cell Lines as Tumor Models for Suicide Gene Therapy
Marlon R. Veldwijk^{a, b}, Simone Berlinghoff^b, Anna Jauch^c, Stephanie Laufs^b, Jens Zeller^b, Frederik Wenz^a, Stefan Fruehauf^d

^a Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim,
^bResearch Program Translational Cancer Research, German Cancer Research Center, INF 280, Heidelberg,
^c Institute of Human Genetics, University of Heidelberg, INF 366, Heidelberg,
^dDepartment of Internal Medicine V, University of Heidelberg, INF 410, Heidelberg,
^e Center for Tumor Diagnostics and Therapy, Paracelsus Klinik, Osnabrück, Germany

Address of Corresponding Author

Onkologie 2008;31:91-96 (DOI: 10.1159/000113504)

Key Words

Mesothelioma
FISH
Adeno-associated virus
Mouse model
Suicide gene therapy

Summary

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.

Author Contacts

Prof. Dr. Stefan Fruehauf,Zentrum für Tumordiagnostik und -therapie Paracelsus Klinik,Am Natruper Holz 69, 49076 Osnabrück, Germany,Tel. +49 541 966-3040, Fax -3046,E-mail prof.stefan.fruehauf@pk-mx.de

Article Information

Published online: February 8, 2008
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 2, Number of References : 30

Medline Abstract (ID 18322411)

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