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- W2070468980 abstract "The lectin from Canavalia ensiformis (Concanavalin-A, ConA), one of the most abundant lectins known, enables one to mimic biological lectin/carbohydrate interactions that regulate extracellular matrix protein recognition. As such, ConA is known to induce membrane type-1 matrix metalloproteinase (MT1-MMP) and is, therefore, routinely used to assess MT1-MMP-mediated functions. Given that gliomas with increasing histological grade demonstrated MT1-MMP expression that correlated with high expression of cyclooxygenase (COX)-2, we specifically assessed the early proinflammatory cellular signaling processes triggered by ConA, a lectin known to induce MT1-MMP expression, in the regulation of COX-2. We found that treatment with ConA or direct overexpression of a recombinant MT1-MMP resulted in the induction of COX-2 expression. This increase in COX-2 was correlated with a concomitant decrease in phosphorylated AKT suggestive of cell death induction, and was independent of MT1-MMP9s catalytic function. ConA and MT1-MMP-mediated intracellular signaling and induction of COX-2 was also validated in both wild-type and Nuclear Factor-kappaB (NF-κB) p65 −/− mutant mouse embryonic fibroblasts (MEF), but was abrogated in NF-κB1 (p50) −/− and in I kappaB kinase (IKK) γ −/− mutant MEF cells. Collectively, our results highlight an IKK/NF-κB-dependent pathway linking MT1-MMP-mediated intracellular signaling to the induction of COX-2 by ConA. That signaling pathway could account for the inflammatory balance responsible for the therapy resistance phenotype of glioblastoma cells, and prompts for the design of new therapeutic strategies that target cell surface carbohydrate structures and MT1-MMP-mediated signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4027." @default.
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- W2070468980 date "2010-04-15" @default.
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- W2070468980 title "Abstract 4027: The lectin concanavalin-A induces cyclooxygenase-2 expression through an IKKgamma/NFkB-dependent pathway in U87 glioblastoma cells" @default.
- W2070468980 doi "https://doi.org/10.1158/1538-7445.am10-4027" @default.
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