Project description:miRNA sequencing data from immortalized murine astrocytes cocultured with U87 cells to evaluate transfer of miRNA from GBM to astrocytes
Project description:<p>Macrophages are prominent immune cells in the tumor microenvironment that can be educated into pro-tumoral phenotype by tumor cells to favor tumor growth and metastasis. The mechanisms that mediate a mutualistic relationship between tumor cells and macrophages remain poorly characterized. Here, we have shown <em>in vitro</em> that different human and murine cancer cell lines release branched‐chain α‐ketoacids (BCKAs) into the extracellular milieu, which influence macrophage polarization in an monocarboxylate transporter 1 (MCT1)‐dependent manner. We found that α‐ketoisocaproate (KIC) and α‐keto‐β‐methylvalerate (KMV) induced a pro‐tumoral macrophage state, whereas α‐ketoisovalerate (KIV) exerted a pro‐inflammatory effect on macrophages. This process was further investigated by a combined metabolomics/proteomics platform. KMV and KIC altered macrophage tricarboxylic acid (TCA) cycle intermediates and increased polyamine metabolism. Proteomic and pathway analyses revealed that the three BCKAs, especially KMV, exhibited divergent effects on the inflammatory signal pathways, phagocytosis, apoptosis and redox balance. These findings uncover cancer‐derived BCKAs as novel determinants for macrophage polarization with potential to be selectively exploited for optimizing antitumor immune responses.</p>
Project description:To investigate the altered gene expression levels in chondrocytes cocultured with BMSCs. Each group had a biological repeat (n=3). Results provide insight into the effect of chondrocytes cocultured with bone marrow stem cells
Project description:Inhibitors of Wnt signaling have been previously shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts (OBSOSTKO) promotes PC invasion while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells as quantified by TOPFLASH reporter and b-catenin activity, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts up-regulated under highly invasive conditions. Following further analysis we found that CRIM1 increases PC3 invasion, complexes with b-catenin, and promotes cell-adhesion, suggesting that elevated Wnt signaling secreted from the bone may promote PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of metastatic cancer cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via tail vein did not readily metastasize in NSG xenografts, suggesting that targeting the molecular bone environment may influence bone metastatic outcome in clinical settings. PC3 cells were cultured for 48 hours in specified conditions prior to RNA extraction and hybridization on Affymetrix Human Genome U133 Plus 2.0 Array. All experiments were performed in at least duplicates. Total RNA was collected from PC3 cells cultured in normal growth media, cocultured with WT mouse osteoblasts supplemented with recombinant human DKK1, cells cocultured with WT mouse osteoblasts supplemented with recombinant human SOST, or cocultured with SostKO mouse osteoblasts.
Project description:To investigate the gene expression of lung epithelial cells effected by Trichomonas tenax, we chose A549 lung epithelial cells and cocultured with Trichomonas tenax at MOI1.
Project description:Huh6 and Hep-G2 were co-cultured with macrophages directly. NCI-H23 was co-cultured with conditional medium of macrophages and SPP1(osteopontin).
Project description:To investigate the gene expression of lung epithelial cells effected by Trichomonas tenax, we chose NCI-H292 lung epithelial cells and cocultured with Trichomonas tenax.