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CD133 activates IL-1 signaling to induce EMT and invasion in pancreatic cancer
Abstract   Peer reviewed

CD133 activates IL-1 signaling to induce EMT and invasion in pancreatic cancer

Alice Nomura, Shrey Modi, Vikas Dudeja, Ashok Saluja and Sulagna Banerjee
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], Vol.15(3 Suppl), pp.S41-S41
06/01/2015
DOI: 10.1016/j.pan.2015.05.172

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Abstract

Introduction: CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer. We and others have recently shown that CD133 does indeed play a functional role in the Epithelial-Mesenchymal Transition (EMT), invasion, and metastasis of pancreatic cancer. Aims: The aim of this study was to determine the role of CD133-mediated IL-1 signaling in pancreatic cancer. Patients & methods: CD133 overexpression and silencing techniques were used in several established pancreatic ductal adenocarcinoma cell lines with minimal and high populations of CD133+ cells, respectively. CD133+ and CD133- sorted populations were utilized from KPC tumor and KPC tumor derived cell lines. IL-1 signaling was inhibited through silencing of the IL-1 receptor and antagonizing the receptor via IL-1RA. Results: IL-1b expression and secretion positively correlated with levels of CD133 populations in several cell lines (MIA PaCa-2, Capan-1, S2VP10, KPC tumor-derived cell line). Levels and secretion of IL-1b was significantly increased upon overexpression of CD133, leading to increased NF-kB activation, EMT induction, and cellular invasion in vitro. These effects were dependent on IL-1 signaling, as silencing or blocking of IL-1R via siRNA or IL-1RA, respectively, significantly decreased NF-kB activity, EMT transcription factor gene expression, mesenchymal markers (VIM and CDH2), and decreased in vitro cellular invasiveness. Conclusion: CD133 expression mediates the induction of IL-1b signaling and secretion, thereby inducing Epithelial-Mesenchymal Transition and invasion in pancreatic cancer.
Gene Expression Pancreatic Cancer

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