Determination of the Ligand-Binding Specificities of the α2β1 and α1β1 Integrins in a Novel 3-Dimensional In Vitro Model of Pancreatic Cancer

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Abstract
Objectives: Pancreatic cancer cells express 2 known collagen-binding integrins, α2β1 and α1β1. The ligand-binding specificity of α1β1 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 α2β1 and α1β1 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 α2β1-specific manner and that this integrin-specific adhesion is required for subsequent cell proliferation. MiaPaCa-2 cells, which do not express the α2β1 or α1β1 integrins, do not attach or proliferate on 3D type I collagen scaffolds. We also demonstrate the novel finding that the α1β1 integrin is a type IV collagen receptor in pancreatic cancer cells. Conclusions: These data indicate that targeting α2β1 integrin-specific type I collagen adhesion may have therapeutic value in the treatment of pancreatic cancer.

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