Translational Therapeutics

British Journal of Cancer (2006) 94, 1311–1319. doi:10.1038/sj.bjc.6603088 www.bjcancer.com
Published online 4 April 2006

The alpha2bold italic beta1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

J J Grzesiak1 and M Bouvet1

1Department of Surgery (112-E), University of California, Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA

Correspondence: Dr M Bouvet, E-mail: mbouvet@ucsd.edu

Revised 8 February 2006; Accepted 13 March 2006; Published online 4 April 2006.

Top

Abstract

Pancreatic cancer is characterised by a hallmark desmoplastic response that includes upregulated expression of the extracellular matrix, and type I collagen in particular. Recent studies indicate that pancreatic cancer cells stimulate type I collagen synthesis in adjacent stellate cells, and that this upregulated type I collagen expression promotes the malignant phenotype in tumour cells as defined by increased proliferation, resistance to chemically induced apoptosis, and increased tumorigenesis. The integrin specificity of this interaction between type I collagen and tumour cells was not identified, however. In the present study, we examined eight pancreatic cancer cell lines for adhesion, proliferation, and migration, on types I and IV collagen, fibronectin, laminin, and vitronectin, as well as integrin expression. Our results indicate, for the overwhelming majority of cell lines, that type I collagen promotes the strongest adhesion, proliferation, and migration relative to the other substrates tested. Utilising function-blocking monoclonal antibodies directed against particular integrin subunits in cell adhesion and migration inhibition assays, we demonstrate further that the malignant phenotype on type I collagen is mediated specifically by the alpha2beta1 integrin. These results identify alpha2beta1 integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer.

Keywords:

laminin, fibronectin, extracellular matrix, migration, adhesion