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Metastasis-associated proteins, such as S100A4 and MTA1, have been studied for over two decades, but correlation between the two proteins remains obscure. A recent report suggesting that silencing of ...S100A4 in endothelial cells significantly suppresses in vitro tube formation and in vivo tumor angiogenesis, motivated us to examine MTA1 from the same perspective. In this study, we showed that the suppression of MTA1 in endothelial cells by murine MTA1-specific small interference RNA (mMTA1 siRNA) induced inhibition of tube formation in vitro and new blood vessel formation in vivo using Directed In Vivo Angiogenesis Assay (DIVAA). Moreover, we found mMTA1 siRNA inhibited tumor angiogenesis in a xenograft model. Further, we revealed that inhibition of angiogenesis by MTA1 siRNA mediates downregulation of S100A4 followed by promoting phosphorylation of non-muscle myosin IIA (NMIIA) and the signaling might be independent of VEGF/ VEGFR pathway in endothelial cells. These data suggested that silencing of MTA1 in endothelial cells could be used as a new strategy to induce tumor regression, by inhibiting tumor angiogenesis.続きを見る
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