title: Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis.
abstract: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.
authors.affiliation: Department of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, West German Lung Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. Till_ploenes@gmx.de.|Department of Pneumology, Center for Medicine, Medical Center University of Freiburg, Freiburg, Germany. Till_ploenes@gmx.de.
authors.forename: Till
authors.initials: T
authors.lastname: Plönes
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Mitja
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Höhne
authors.affiliation: Graduate School of Pharmaceutical Sciences, Department of Clinical Pharmacology & Pharmacometrics, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8675, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
authors.affiliation: Department of Pneumology, Center for Medicine, Medical Center University of Freiburg, Freiburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D009361:Neoplasm Invasiveness / Q000235:genetics; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology*; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: Asbestos; Cancer; Chemoresistance; Cisplatin; Decortication; Drug; EMT; EPP; Epigenetics; Epithelial to mesenchymal transition; Met; P/D; Pleural; Pleuropneumonectomy; Stem cells; Wilms tumor