The alpha2beta1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines.

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.

journal_name

Br J Cancer

authors

Grzesiak JJ,Bouvet M

doi

10.1038/sj.bjc.6603088

subject

Has Abstract

pub_date

2006-05-08 00:00:00

pages

1311-9

issue

9

eissn

0007-0920

issn

1532-1827

pii

6603088

journal_volume

94

pub_type

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