tenascin-c enhances pancreatic cancer cell growth and motility and affects cell adhesion through activation of the integrin pathwaytenascin-c提高胰腺癌细胞生长和能动性和影响细胞粘附通过整合素的活化途径.pdf

Tenascin-C Enhances Pancreatic Cancer Cell Growth and Motility and Affects Cell Adhesion through Activation of the Integrin Pathway 1,2. 1,2. ¨ ¨ 1 1 3 ¨ 1,2 Igor Paron , Sonja Berchtold , Julia Voros , Madhavi Shamarla , Mert Erkan , Heinz Hofler , Irene Esposito1,2* ¨ 1 Institute of Pathology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, 2 Institute of Pathology, Technische ¨ ¨ ¨ ¨ Universitat Munchen, Munich, Germany, 3 Department of General Surgery, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany Abstract Background: Pancreatic cancer (PDAC) is characterized by an abundant fibrous tissue rich in Tenascin-C (TNC), a large ECM glycoprotein mainly synthesized by pancreatic stellate cells (PSCs). In human pancreatic tissues, TNC expression increases in the progression from low-grade precursor lesions to invasive cancer. Aim of this study was the functional characterization of the effects of TNC on biologic relevant properties of pancreatic cancer cells. Methods: Proliferation, migration and adhesion assays were performed on pancreatic cancer cell lines treated with TNC or grown on a TNC-rich matrix. Stable transfectants expressing the large TNC splice variant were generated to test the effects of endogenous TNC. TNC-dependent integrin signaling was investigated by immunoblotting, immunofluorescence and pharmacological inhibition. Results: Endogenous TNC promoted pancreatic cancer cell growth and migration. A