Determination of the ligand-binding specificities of the alpha2beta1 and alpha1beta1 integrins in a novel 3-dimensional in vitro model of pancreatic cancer.

Abstract

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.

• Authors: John J Grzesiak, Michael Bouvet
• Journal: Pancreas (Pancreas) Vol. 34 Issue 2 Pg. 220-8 (Mar 2007) ISSN: 1536-4828 [Electronic] United States
• PMID: 17312461 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type IV
• Culture Media, Serum-Free
• Glycosaminoglycans
• Integrin alpha1beta1
• Integrin alpha2beta1
• Ligands

Topics

• Adenocarcinoma (metabolism, pathology)
• Cell Adhesion
• Cell Culture Techniques (methods)
• Cell Division
• Cell Line, Tumor
• Collagen Type I (metabolism)
• Collagen Type IV (metabolism)
• Culture Media, Serum-Free
• Glycosaminoglycans (metabolism)
• Humans
• Integrin alpha1beta1 (metabolism)
• Integrin alpha2beta1 (metabolism)
• Ligands
• Pancreatic Neoplasms (metabolism, pathology)
• Protein Binding