Pancreatic Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreatic Cancer, including details on symptoms, causes, treatment, information. | ||||||||
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Determination of the ligand-binding specificities of the alpha2beta1 and alpha1beta1 integrins in a novel 3-dimensional in vitro model of pancreatic cancer.Grzesiak JJ, Bouvet M Department of Surgery, University of California San Diego, San Diego, CA, USA. OBJECTIVES: Pancreatic cancer cells express 2 known collagen-binding integrins, alpha2beta1 and alpha1beta1. The ligand-binding specificity of alpha1beta1 and the integrin/s responsible for mediating the malignant phenotype on type I collagen in the 3-dimensional (3D) tumor microenvironment have not been determined in pancreatic cancer. The aim of the present study was to determine the ligand-binding specificities of the alpha2beta1 and alpha1beta1 integrins using a novel 3D in vitro model of pancreatic cancer. METHODS: We used 3D type I collagen-glycosaminoglycan scaffolds in adhesion and proliferation assays with pancreatic cancer cell lines, as well as affinity chromatography and inhibition of adhesion assays. RESULTS: We demonstrate for the first time that CFPAC, BxPC-3, Colo-357, FG, and Panc-1 cells attach to 3D type I collagen scaffolds in an alpha2beta1-specific manner and that this integrin-specific adhesion is required for subsequent cell proliferation. MiaPaCa-2 cells, which do not express the alpha2beta1 or alpha1beta1 integrins, do not attach or proliferate on 3D type I collagen scaffolds. We also demonstrate the novel finding that the alpha1beta1 integrin is a type IV collagen receptor in pancreatic cancer cells. CONCLUSIONS: These data indicate that targeting alpha2beta1 integrin-specific type I collagen adhesion may have therapeutic value in the treatment of pancreatic cancer. Published 21 February 2007 in Pancreas, 34(2): 220-8.
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