期刊
BRITISH JOURNAL OF CANCER
卷 94, 期 9, 页码 1311-1319出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6603088
关键词
laminin; fibronectin; extracellular matrix; migration; adhesion
类别
资金
- NCI NIH HHS [R33 CA109949, R21 CA109949, CA109949-01] Funding Source: Medline
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 a2b1 integrin. These results identify alpha(2)beta(1) integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据