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Int. J. Mol. Sci. 2017, 18(4), 716;

Endogenously Expressed IL-4Rα Promotes the Malignant Phenotype of Human Pancreatic Cancer In Vitro and In Vivo

Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng, Beijing 100034, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editors: Srikumar Chellappan and Jaya Padmanabhan
Received: 29 December 2016 / Revised: 17 March 2017 / Accepted: 21 March 2017 / Published: 28 March 2017
(This article belongs to the Special Issue Pancreatic Disorders)
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Exogenous interleukin-4 (IL-4) has been demonstrated to affect the growth of different human malignancies including pancreatic cancer cells. The aim of our study was to determine the role of endogenously expressed IL-4-receptor-α-chain (IL-4Rα) in pancreatic cancer cells. IL-4Rα-suppression was achieved by generating Capan-1 cells stably expressing shRNA targeting IL-4Rα. The malignant phenotype was characterized by assessing growth properties, directional and non-directional cell movement in vitro and tumor growth in vivo. Signaling pathways were analyzed upon IL-4 and IL-13 stimulation of wildtype (WT) and control-transfected cells compared to IL-4Rα-knockdown cells. Silencing of IL-4Rα resulted in reduced anchorage-dependent cell growth (p < 0.05) and reduced anchorage-independent colony size (p < 0.001) in vitro. Moreover, cell movement and migration was inhibited. IL-4 and IL-13 stimulation of Capan-1-WT cells induced activation of similar pathways like stimulation with Insulin-like growth factor (IGF)-I. This activation was reduced after IL-4Rα downregulation while IGF-I signaling seemed to be enhanced in knockdown-clones. Importantly, IL-4Rα silencing also significantly suppressed tumor growth in vivo. The present study indicates that endogenously expressed IL-4 and IL-4Rα contribute to the malignant phenotype of pancreatic cancer cells by activating diverse pro-oncogenic signaling pathways. Addressing these pathways may contribute to the treatment of the disease. View Full-Text
Keywords: interleukin-4-receptor; IL-4-receptor-α-chain; IL-13-receptor-α1-chain; interleukin-4; pancreatic cancer interleukin-4-receptor; IL-4-receptor-α-chain; IL-13-receptor-α1-chain; interleukin-4; pancreatic cancer

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Traub, B.; Sun, L.; Ma, Y.; Xu, P.; Lemke, J.; Paschke, S.; Henne-Bruns, D.; Knippschild, U.; Kornmann, M. Endogenously Expressed IL-4Rα Promotes the Malignant Phenotype of Human Pancreatic Cancer In Vitro and In Vivo. Int. J. Mol. Sci. 2017, 18, 716.

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