title: Endogenously Expressed IL-4Rα Promotes the Malignant Phenotype of Human Pancreatic Cancer In Vitro and In Vivo.
abstract: 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.
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. benno.traub@uniklinik-ulm.de.
authors.forename: Benno
authors.initials: B
authors.lastname: Traub
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. sunliemd@126.com.|Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng, Beijing 100034, China. sunliemd@126.com.
authors.forename: Lie
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. mys870311@sina.com.|Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng, Beijing 100034, China. mys870311@sina.com.
authors.forename: Yongsu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. pegfei.xu@uniklinik-ulm.de.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. johannes.lemke@uniklinik-ulm.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lemke
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. stephan.paschke@uniklinik-ulm.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Paschke
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. doris.henne-bruns@uniklinik-ulm.de.
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. uwe.knippschild@uniklinik-ulm.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
authors.affiliation: Department of General and Visceral Surgery, University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany. marko.kornmann@uniklinik-ulm.de.
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics*; D051379:Mice; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: C508596:IL3 protein, human; C508598:IL4 protein, human; C504000:IL4R protein, human; D007377:Interleukin-3; D053662:Interleukin-4 Receptor alpha Subunit; D034741:RNA, Small Interfering; D015847:Interleukin-4
keywords: IL-13-receptor-α1-chain; IL-4-receptor-α-chain; interleukin-4; interleukin-4-receptor; pancreatic cancer