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  • A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns

    Author(s)
    Loessner, Daniela
    Rockstroh, Anja
    Shokoohmand, Ali
    Holzapfel, Boris M
    Wagner, Ferdinand
    Baldwin, Jeremy
    Boxberg, Melanie
    Schmalfeldt, Barbara
    Lengyel, Ernst
    Clements, Judith A
    Hutmacher, Dietmar W
    Griffith University Author(s)
    Hutmacher, Dietmar W.
    Shokoohmand, Ali
    Year published
    2019
    Metadata
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    Abstract
    Peritoneal invasion through the mesothelial cell layer is a hallmark of ovarian cancer metastasis. Using tissue engineering technologies, we recreated an ovarian tumor microenvironment replicating this aspect of disease progression. Ovarian cancer cell-laden hydrogels were combined with mesothelial cell-layered melt electrospun written scaffolds and characterized with proliferation and transcriptomic analyses and used as intraperitoneal xenografts. Here we show increased cancer cell proliferation in these 3D co-cultures, which we validated using patient-derived cells and linked to peritoneal tumor growth in vivo. Transcriptome-wide ...
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    Peritoneal invasion through the mesothelial cell layer is a hallmark of ovarian cancer metastasis. Using tissue engineering technologies, we recreated an ovarian tumor microenvironment replicating this aspect of disease progression. Ovarian cancer cell-laden hydrogels were combined with mesothelial cell-layered melt electrospun written scaffolds and characterized with proliferation and transcriptomic analyses and used as intraperitoneal xenografts. Here we show increased cancer cell proliferation in these 3D co-cultures, which we validated using patient-derived cells and linked to peritoneal tumor growth in vivo. Transcriptome-wide expression analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as bidirectional factors deregulated in 3D co-cultures compared to 3D mono-cultures, which we confirmed by immunohistochemistry of xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. These factors were further increased upon expression of kallikrein-related proteases. This clinically predictive model allows us to mimic the complexity and processes of the metastatic disease that may lead to therapies that protect from peritoneal invasion or delay the development of metastasis.
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    Journal Title
    BIOMATERIALS
    Volume
    190
    DOI
    https://doi.org/10.1016/j.biomaterials.2018.10.014
    Subject
    Oncology and carcinogenesis
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/385750
    Collection
    • Journal articles

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