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A tissue-engineered mimic of the ovarian cancer microenvironment of increases cell proliferation and tumor growth.

ABSTRACT: Using tissue engineering technologies, we aimed to engineer the ovarian tumor microenvironment to study disease progression by combining biomimetic hydrogels with melt electrospun written scaffolds. 3D co-cultures were constructed by assembling ovarian cancer cell-laden hydrogels with mesothelial cell-layered scaffolds. 3D constructs were characterised by proliferation and transcriptomic analyses and applied to an intraperitoneal xenograft model. Increased cancer cell proliferation upon 3D co-cultures was validated using patient-derived cells and linked to greater tumor burden in vivo. Genome-wide microarray analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as being upregulated in 3D co-cultures compared to 3D mono-cultures. Protein expression of these differentially regulated factors was confirmed by immunohistochemistry in xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. This pre-clinical cancer model harbors the complexity of the disease seen in patients and advances our understanding of the underlying cell biology and the contribution of the tumor microenvironment to cancer growth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109577 | GEO | 2018/01/25

REPOSITORIES: GEO

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