A cellular model reflecting the phenotypic heterogeneity of mutant HRAS driven squamous cell carcinoma

Neus Cantariño, M. Teresa Fernández-Figueras, Vanesa Valero, Eva Musulén, Roberto Malinverni, Isabel Granada, Stephen J. Goldie, Juan Martín-Caballero, Julien Douet, Sonia Vanina Forcales, Marcus Buschbeck

    Research output: Contribution to journalArticleResearchpeer-review

    9 Citations (Scopus)

    Abstract

    © 2016 UICC. Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics. We observed three major tissue architectures: solid, sarcomatoid and cystic growth types, which were primarily composed of pleomorphic and basaloid cells but in some cases displayed focal apocrine differentiation. We demonstrate that the cells generated represent different stages of skin cancerogenesis and as such can be used to identify novel tumor-promoting alterations such as the overexpression of the PADI2 oncogene in solid-type SCC. Importantly, the cultured cells maintain the characteristics from the xenograft they were derived from while being amenable to manipulation and analysis. The availability of cell lines representing different clinical manifestations opens a new tool to study the stochastic and deterministic factors that cause case-to-case heterogeneity despite departing from the same set of oncogenes and the same genetic background.
    Original languageEnglish
    Pages (from-to)1106-1116
    JournalInternational Journal of Cancer
    Volume139
    Issue number5
    DOIs
    Publication statusPublished - 1 Sep 2016

    Keywords

    • cell culture and xenograft model
    • squamous cell carcinoma
    • tumour heterogeneity

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