Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma

Amanda Hudson, Chris Weir, Elizabeth Moon, Rozelle Harvie, Sonja Klebe, Stephen Clarke, Nick Pavlakis, Viive Howell

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16 INK4A/p14 ARF and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies.

    Original languageEnglish
    Article number6152
    Pages (from-to)Article: 6152
    Number of pages11
    JournalScientific Reports
    Volume4
    DOIs
    Publication statusPublished - 21 Aug 2014

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