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  • The EMBO Journal (2007) 26, 2832 - 2842
  • doi:10.1038/sj.emboj.7601738

Published online: 31 May 2007

Increased tumor cell dissemination and cellular senescence in the absence of bold beta1-integrin function

Angelika Kren1, Vanessa Baeriswyl1, François Lehembre1, Christoph Wunderlin1, Karin Strittmatter1, Helena Antoniadis1, Reinhard Fässler2, Ugo Cavallaro3 and Gerhard Christofori1

  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

Correspondence to:

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

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 beta cell carcinogenesis to investigate the role of beta1-integrin in tumor progression. Specific ablation of beta1-integrin function in pancreatic beta cells resulted in a defect in sorting between insulin-expressing beta cells and glucagon-expressing alpha cells in islets of Langerhans. Ablation of beta1-integrin in beta 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 beta1-integrin-deficient beta 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 beta1-integrin-deficient beta tumor cells. The results indicate a critical role of beta1-integrin function in mediating metastatic dissemination and preventing tumor cell senescence.

  • Keywords:

    • cell adhesion,
    • beta1-integrin,
    • metastasis,
    • senescence,
    • tumorigenesis