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Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

  • Blum, Walter Anatomy, Department of Medicine, University of Fribourg, Switzerland
  • Schwaller, Beat Anatomy, Department of Medicine, University of Fribourg, Switzerland
    2013
Published in:
  • International Journal of Cancer. - 2013, p. –
English Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy-resistance and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma, but still little is known about CR's putative function(s) in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway and furthermore, SV40 early region genes are able to up-regulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Down-regulation of CR via lentiviral-mediated shRNA significantly decreased the viability and proliferation of mesothelioma cells in vitro. The effect was strong in epithelioid-dominated cell lines (ZL55, MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212, ZL34). The specificity of the effect was confirmed by stable eGFP-CR expression in mesothelioma cell lines and subsequent down-regulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72h post-infection via strong activation of the intrinsic caspase 9-dependent pathway. Down-regulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G₁ block without decreasing viability or activating apoptosis pathways. Our results demonstrate that down-regulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from malignant mesothelioma. We anticipate these findings to reveal calretinin as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, but also of the mixed and sarcomatoid type.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/303021
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