62 research outputs found

    Mesenchymal Stem Cells in Early Entry of Breast Cancer into Bone Marrow

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    BACKGROUND: An understanding of BC cell (BCC) entry into bone marrow (BM) at low tumor burden is limited when compared to highly metastatic events during heavy tumor burden. BCCs can achieve quiescence, without interfering with hematopoiesis. This occurs partly through the generation of gap junctions with BM stroma, located close to the endosteum. These events are partly mediated by the evolutionary conserved gene, Tac1. METHODOLOGY/PRINCIPAL FINDINGS: This study focuses on the role of mesenchymal stem cells (MSCs), Tac1, SDF-1 and CXCR4 in BCC entry into BM. The model is established in studies with low numbers of tumor cells, and focuses on cancer cells with low metastatic and invasion potential. This allowed us to recapitulate early event, and to study cancer cells with low invasive potential, even when they are part of larger numbers of highly metastatic cells. A novel migration assay showed a facilitating role of MSCs in BCC migration across BM endothelial cells. siRNA and ectopic expression studies showed a central role for Tac1 and secondary roles for SDF-1alpha and CXCR4. We also observed differences in the mechanisms between low invasive and highly metastatic cells. The in vitro studies were verified in xenogeneic mouse models that showed a preference for low invasive BCCs to BM, but comparable movement to lung and BM by highly metastatic BCCs. The expressions of Tac1 and production of SDF-1alpha were verified in primary BCCs from paired samples of BM aspirates and peripheral blood. CONCLUSIONS/SIGNIFICANCE: MSC facilitate BCC entry into BM, partly through Tac1-mediated regulation of SDF-1alpha and CXCR4. We propose a particular population of BCC with preference for BM could be isolated for characterization. This population might be the subset that enter BM at an early time period, and could be responsible for cancer resurgence and resistance to current therapies

    Effects of Nanoporous and Microgrooved Substrates on Cell Morphology and Cell Migration of Hepatoma Cells

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    Understanding the mechanism of how surface topography influences mammalian cells is important for the development of medical implants and tissue engineering. Although variety of cell types have been used in cell-substrate studies for different purposes, hepatocytes have been paid relatively less attention. In this study, we investigated the influences of nanopores and microgrooves on the morphology and migration of hepatoma cell line, BEL-7402 cells. The cells were cultured on different synthetic substrates including flat cell culture plate, flat silicon wafer sputtered with alumina, nanoporous (140 nm in diameter) anodized aluminum membrane (AAM) surface, flat polydimethylsiloxane (PDMS), and PDMS patterned with microgrooves of various widths (10 μm, 30 μm and 50 μm in width, and 2 μm in depth). Cellular behaviour on these surfaces was studied using fluorescent microscopy, time lapse microscopy and scanning electron microscopy (SEM)

    Effects of Nanoporous and Microgrooved Substrates on Cell Morphology and Cell Migration of Hepatoma Cells

    Get PDF
    Understanding the mechanism of how surface topography influences mammalian cells is important for the development of medical implants and tissue engineering. Although variety of cell types have been used in cell-substrate studies for different purposes, hepatocytes have been paid relatively less attention. In this study, we investigated the influences of nanopores and microgrooves on the morphology and migration of hepatoma cell line, BEL-7402 cells. The cells were cultured on different synthetic substrates including flat cell culture plate, flat silicon wafer sputtered with alumina, nanoporous (140 nm in diameter) anodized aluminum membrane (AAM) surface, flat polydimethylsiloxane (PDMS), and PDMS patterned with microgrooves of various widths (10 μm, 30 μm and 50 μm in width, and 2 μm in depth). Cellular behaviour on these surfaces was studied using fluorescent microscopy, time lapse microscopy and scanning electron microscopy (SEM)
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