Angiopoietin-1 and -2 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis

Fagiani, E. and Lorentz, P. and Kopfstein, L. and Christofori, G.. (2011) Angiopoietin-1 and -2 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis. Cancer research, Vol. 71, H. 17. pp. 5717-5727.

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Official URL: http://edoc.unibas.ch/dok/A6003449

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Members of the Angiopoietin family regulate various aspects of physiologic and pathologic angiogenesis. Although Angiopoietin-1 (Ang-1) decreases endothelial cell permeability and increases vascular stabilization via recruitment of pericytes and smooth muscle cells to growing blood vessels, Angiopoietin-2 (Ang-2) mediates angiogenic sprouting and vascular regression. In this study, we used the Rip1Tag2 transgenic mouse model of pancreatic ?-cell carcinogenesis to investigate the roles of Ang-1 and Ang-2 in tumor angiogenesis and tumor progression. On their own, transgenic expression of human Ang-1 or Ang-2 in pancreatic ? cells caused formation of peri-insular lymphatic vessels in the absence of effects on blood vessel density, islet morphology, or physiology. When crossed to Rip1Tag2 mice, both Ang-1-and Ang-2-expressing ?-cell tumors showed increased peritumoral lymphangiogenesis in the absence of metastasis to local lymph nodes or distant organs. There was no alteration in tumor outgrowth, blood vessel density, or vessel maturation in Ang-1-expressing tumors. In contrast, Ang-2-expressing tumors exhibited diminished pericyte recruitment to blood vessels that were dilated, nonfunctional, and highly permeable. These tumors were hemorrhagic, highly infiltrated by leukocytes, and impaired in outgrowth. Together, our findings establish that Ang-2 antagonizes Ang-1 function, leading to excessive vessel sprouting with impaired pericyte recruitment and vessel stabilization. The poor perfusion of immature blood vessels results in retarded tumor growth, defining an important pathophysiologic pathway required for efficient tumorigenesis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:13 Sep 2013 07:49

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