Neue Therapiekonzepte


A successful systemic therapy for human pancreatic cancer is currently not available. Although extensive stroma deposition and dense vascularization are well established characteristics of human pancreatic cancer, little is known about their functional relationship. We have established an orthotopic mouse model of human pancreatic cancer disease, which mimics important clinical features such as hem- and lymphangiogenesis as well as metastasis. In response to overexpression of proangiogenic factors of the angiopoetin family in this model, we have observed changes in integrin expression and adhesion in vitro. Using pharmacological integrin inhibitors, the contribution of these alterations for tumor growth in vivo will be determined. Furthermore, we will address the question whether, conversely, the expression of proangiogenic factors is regulated by tumor cell matrix interactions, i.e. via integrins. To experimentally address this issue, we have already established cell lines with modifications in their integrin expression pattern. Insights into the functional interaction of the stroma and the vascular compartment may allow to optimize antiangiogenic therapy for pancreatic cancer.
Head of Project:

Univ. Prof. Dr. Bertram Wiedenmann
Charité - Universitätsmedizin Berlin
Department of Internal Medicine, Hepatology and Gastroenterology (incl. Metabolic Diseases) CVK
Tel. 450-553022
Fax 450-553901
bertram.wiedenmann@charite.de
Additional Member of Project:

Dr. K. Detjen, Dr. A. Scholz, Dr. K. Wagner, I. Eichhorn, Y. Giesecke, M. Schröder,
Begin/End of Project:

09/2005 - 12/2010
Funded by:

Jerini AG
Publications:

1. Von Marschall Z., Scholz A., Stacker S.A., Achen M.G., Jackson D.G., Alves F., Schirner M., Haberey M., Thierauch K.H., Wiedenmann B. & Rosewicz S.: Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. Int J Oncol: 27(3) 669-79, 2005 2. Tumor suppressor p16INK4a--modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells.André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, Wiedenmann B, von Knebel Doeberitz M, Gress TM, Nishimura S, Rosewicz S, Gabius HJ. 3. Galectin-1 interacts with the {alpha}5{beta}1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p27.Fischer C, Sanchez-Ruderisch H, Welzel M, Wiedenmann B, Sakai T, André S, Gabius HJ, Khachigian L, Detjen KM, Rosewicz S. J Biol Chem. 2005 Nov 4;280(44):37266-77.