Increased tumor cell dissemination and cellular senescence in the absence of beta1-integrin function.
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 beta(1)-integrin in tumor progression. Specific ablation of beta(1)-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 beta(1)-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 beta(1)-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 beta(1)-integrin-deficient beta tumor cells. The results indicate a critical role of beta(1)-integrin function in mediating metastatic dissemination and preventing tumor cell senescence.
Kren
Angelika
A
Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
Baeriswyl
Vanessa
V
Lehembre
François
F
Wunderlin
Christoph
C
Strittmatter
Karin
K
Antoniadis
Helena
H
Fässler
Reinhard
R
Cavallaro
Ugo
U
Christofori
Gerhard
G
D000818:Animals; D002469:Cell Separation; D016922:Cellular Senescence; D005434:Flow Cytometry; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction
D019012:Integrin beta1