Determination of the ligand-binding specificities of the α2β1 and α1β1 integrins in a novel 3-dimensional in vitro model of pancreatic cancer

Objectives: Pancreatic cancer cells express 2 known collagen-binding integrins, alpha(2)beta(1) and alpha(1)beta(1). The ligand-binding specificity of alp, 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 alpha(2)beta(1), and alpha(1)beta(1) integrins using a novel 3D 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 alpha(2)beta(1)-specific manner and that this integrin-specific adhesion is required for subsequent cell proliferation. MiaPaCa-2 cells, which do not express the alpha(2)beta(1) or alpha(1)beta(1) integrins, do not attach or proliferate on 3D type 1 collagen scaffolds. We also demonstrate the novel finding that the alpha(1)beta(1) integrin is a type IV collagen receptor in pancreatic cancer cells. Conclusions: These data indicate that targeting alpha(2)beta(1) integrin-specific type I collagen adhesion may have therapeutic value in the treatment of pancreatic cancer.