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| Subject Categories: Cell & Tissue Architecture | Molecular Biology of Disease |
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| The EMBO Journal
(2007) 26, 2832–2842, doi:10.1038/sj.emboj.7601738 Published online 31 May 2007 |
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Increased tumor cell dissemination and cellular senescence in the absence of  1-integrin function |
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| Angelika Kren1, Vanessa Baeriswyl1, François Lehembre1, Christoph Wunderlin1, Karin Strittmatter1, Helena Antoniadis1, Reinhard Fässler2, Ugo Cavallaro3 and Gerhard Christofori1 |
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1 Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, Switzerland 2 Max-Planck-Institute of Biochemistry, Department of Molecular Medicine, Martinsried, Germany 3 IFOM-FIRC Institute of Molecular Oncology, Milano, Italy To whom correspondence should be addressed Gerhard Christofori, Institute of Biochemistry and Genetics, Department of Clinical Biological Sciences, Center of Biomedicine, University of Basel, Mattenstrasse 28, Basel 4058, Switzerland. Tel.: +41 61 267 3564; Fax: +41 61 267 3566; E-mail: Gerhard.Christofori@unibas.ch Received 24 December 2006; Accepted 8 May 2007; Published online 31 May 2007. |
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| Abstract |
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Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization, as well as transduction of signals into cells, to promote various aspects of cellular behavior, such as proliferation or survival. Integrins participate in many aspects of tumor biology. Here, we have employed the Rip1Tag2 transgenic mouse model of pancreatic cell carcinogenesis to investigate the role of 1-integrin in tumor progression. Specific ablation of 1-integrin function in pancreatic cells resulted in a defect in sorting between insulin-expressing cells and glucagon-expressing  cells in islets of Langerhans. Ablation of 1-integrin in tumor cells of Rip1Tag2 mice led to the dissemination of tumor cell emboli into lymphatic blood vessels in the absence of ongoing lymphangiogenesis. Yet, disseminating 1-integrin-deficient tumor cells did not elicit metastasis. Rather, primary tumor growth was significantly impaired by reduced tumor cell proliferation and the acquisition of cellular senescence by 1-integrin-deficient tumor cells. The results indicate a critical role of 1-integrin function in mediating metastatic dissemination and preventing tumor cell senescence. |
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| Keywords: cell adhesion, 1-integrin, metastasis, senescence, tumorigenesis |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHRat neonatal immune challenge alters adult responses to cerebral ischaemia Journal of Cerebral Blood Flow & Metabolism Original Article Journal of Cerebral Blood Flow & Metabolism Original Article Increased tumor cell dissemination and cellular senescence in the absence of β 1 -integrin function The EMBO Journal Article |
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