Determination of the ligand-binding specificities of the alpha2beta1 and alpha1beta1 integrins in a novel 3-dimensional in vitro model of pancreatic cancer.
OBJECTIVE
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.
Grzesiak
John J
JJ
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Bouvet
Michael
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D016895:Culture Media, Serum-Free; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008024:Ligands; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding
D024042:Collagen Type I; D024141:Collagen Type IV; D016895:Culture Media, Serum-Free; D006025:Glycosaminoglycans; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D008024:Ligands