29 research outputs found

    Proteolytically degradable PEG hydrogel matrix mimicking tumor immune microenvironment for 3D co-culture of lung adenocarcinoma cells and macrophages

    No full text
    Tumor-associated macrophages and monocytes are the major stromal cell types found in the tumor immune microenvironment (TIME), which modulates tumor progression, invasion, and chemoresistance. To address the need for an in vitro three-dimensional tumor model for understanding the complex cellular interactions within the TIME, we propose a TIME-mimetic co-culture matrix composed of photo-crosslinked poly(ethylene glycol) hydrogels mimicking the characteristics of the tumor and stroma. Desmoplasia-mimetic microgels encapsulating lung adenocarcinoma cells (A549) were embedded with monocyte- or macrophage-type U937 cells in normal stroma-mimetic hydrogel, increasing the proximity between the two cell types. By modulating the proteolytic degradability of the hydrogels, we could separate different cell types with high purities for use in orthogonal assays. In addition, we demonstrated that U937 cells had distinct influences on A549 cell death depending on their activation states (i.e. monocyte, M0, or M1 phenotype). M1 macrophages suppressed tumor growth and increased the susceptibility of A549 cells to cisplatin. In contrast, monocytes upregulated cancer stem cell markers (OCT4, SOX2, and SHH) of A549 cells, showing M2-like features, such as downregulated expression of proinflammatory markers (IL6 and TNFα). These findings suggest that this co-culture system is potentially used for investigation of heterotypic cellular interactions in the TIME. The developed co-culture model successfully reproduces complex tumor immune microenvironment.The model is composed of tumor- and stroma-mimetic matrices containing tumor and immune cells.Sequential matrix degradation enabled the independent cell collection. The developed co-culture model successfully reproduces complex tumor immune microenvironment. The model is composed of tumor- and stroma-mimetic matrices containing tumor and immune cells. Sequential matrix degradation enabled the independent cell collection.</p

    Functional annotation networks consisting of biological pathways enriched with TWAS genes for UF.

    No full text
    (A) Four major clusters grouped into three parental biological pathways were enriched with positively associated TWAS genes (TWAS P-value 0). (B) Four major clusters of biological pathways were enriched with negatively associated TWAS genes (TWAS P-value < 0.05 and Z-score < 0). The major clusters are the sub-networks in the top 25% for connectivity score as calculated by the MCODE in each functional annotation network. Each node represented by a pie chart indicates an enriched biological pathway, and the sector size is proportional to the number of genes that originate from each tissue panel. The node size corresponds to the number of panels where TWAS genes were enriched.</p

    A list of five toxic chemicals discovered based on CTD as potentially toxic chemicals for UF.

    No full text
    A list of five toxic chemicals discovered based on CTD as potentially toxic chemicals for UF.</p

    A list of significant TWAS genes associated with UF (P < 1.90 × 10<sup>−6</sup>).

    No full text
    A list of significant TWAS genes associated with UF (P −6).</p

    Circos plots showing how marginally significant TWAS gene lists (P < 0.05) for each of the eight eQTL panels overlap.

    No full text
    On the outside, the arc represents the eight eQTL panels. On the inside, the dark orange arc represents genes shared by several panels and the light orange arc represents genes unique to those panels. The purple lines link the genes shared by several panels. (A) The plot shows the shared genes between positively associated TWAS genes (TWAS Z-score > 0). (B) The plot shows shared genes between negatively associated TWAS genes (TWAS Z-score (TIF)</p

    A ternary plot of colocalization test results.

    No full text
    PP0–4 indicate PPs of five hypotheses (H0–4). The gray dots are the genes that were not significant in either TWAS or the colocalization tests. The red and blue dots indicate the significantly associated genes in TWAS and the colocalization tests, respectively. The genes that were prioritized in both TWAS and the colocalization tests are represented as purple dots. (TIFF)</p
    corecore