In addition, our results clearly indicate that the perception of a COX2/PGE2-driven VEGFA expression, sustaining neo-angiogenesis, is an oversimplification. O88 Tenascin-C in the Tumor Microenvironment Triggers Oncogenic Signaling Yundan Jia1,2, Isabelle Gasser1, Caroline Spenle1, Martial Kammerer1, Falk Doxorubicin clinical trial Saupe1, Marija Marko1, Jessica Kant1, Valentin Djonov3, Klaus-Peter Janssen4, Anne-Catherine Feutz2, Michael van der Heyden1, Wentao Huang2, Patricia Simon-Assmann1, Michèle Kedinger1, Agnes Neuville-Mechine5, Gerhard Christofori2, Gertraud Orend 1,2 1 Inserm U682, Tissue Homeostasis

in Inflammation and Cancer, Faculté de Médicine, Université de Strasbourg, Strasbourg, France, 2 Institute of Biochemistry and Genetics, Center for Biomedicine,

University of Basel, Basel, Switzerland, 3 Department of Medicine, Gross Anatomy and Vascular Biology, University of Fribourg, Fribourg, Switzerland, 4 Department of Surgery, Technische Universitaet Muenchen, Muenchen, Germany, 5 Hospital Hautepierre, Faculté de Médicine, Université de Strasbourg, Strasbourg, France The extracellular matrix molecule tenascin-C (TNC) is highly expressed in most cancers which correlates with a bad survival prognosis and tamoxifen resistance. TNC plays a role in promoting tumor cell proliferation, angiogenesis, GPCR Compound Library ic50 invasion and metastasis but the molecular mechanisms http://www.selleck.co.jp/products/Nutlin-3.html are poorly understood (1). We showed that TNC induces cell rounding by two mechanisms: it counteracts cell adhesion to fibronectin by blocking the syndecan-4 / integrin alpha 5 beta 1 complex (2). This stimulates tumor cell proliferation (3) by activation of oncogenic Wnt (through repression of DKK1) and MAPkinase signaling (4). TNC also stimulates endothelin receptor type A (EDNRA) expression which maintains cell rounding (5). FAK, paxillin, RhoA and Tropomyosin-1

are critical targets of TNC downstream of syndecan-4 and EDNRA (5, 6). TNC also triggers cell migration in combination with LPA/PDGF (6). Results on the tumorigenesis-promoting effects of TNC in our newly established transgenic mice that ectopically express TNC in the pancreatic islets of insulinoma-prone SV40 Tag-expressing RipTag2 mice (RT2/TNC) will be presented. (Supported by INSERM, INCa, Bourse Region Alsace, Oncosuisse, SNF, ARC, AICR, Krebsliga Beider Basel) References: (1) Orend & Chiquet-Ehrismann, 2006, Cancer Lett. 244, 143 (2) Orend et al., 2003, Oncogene 22, 3917 (3) Huang et al., 2001, Cancer Res. 61, 8586 (4) Ruiz et al., 2004, Cancer Res. 64, 7377 (5) Lange et al., 2007, Cancer Res. 67, 6163 (6) Lange et al., 2008, Cancer Res.