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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4642-4648. Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-08-3327. This Article Full Text (PDF) All Versions of this Article: 2004-08-3327v1 105/12/4642    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tammela, T. Articles by Alitalo, K. Search for Related Content PubMed PubMed Citation Articles by Tammela, T. Articles by Alitalo, K. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 27, 2004 Accepted January 25, 2005 Angiopoietin-1 promotes lymphatic sprouting and hyperplasia Tuomas Tammela, Anne Saaristo, Marja Lohela, Tohru Morisada, Jenny Tornberg, Camilla Norrmen, Yuichi Oike, Katri Pajusola, Gavin Thurston, Toshio Suda, Seppo Yla-Herttuala, and Kari Alitalo* Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA A. I. Virtanen Institute and Department of Medicine, University of Kuopio, Kuopio, Finland * Corresponding author; email: kari.alitalo{at}helsinki.fi. Angiopoietin (Ang) 1, a ligand for the receptor tyrosine kinase Tie2, regulates the formation and stabilization of the blood vessel network during embryogenesis. In adults, Ang1 is associated with blood vessel stabilization and recruitment of perivascular cells, whereas Ang2 acts to counter these actions. Recent results from gene-targeted mice have shown that Ang2 is also essential for the proper patterning of lymphatic vessels and that Ang1 can be substituted for this function. In order to characterize the effects of the angiopoietins on lymphatic vessels, we employed viral vectors for overexpression of Ang1 in adult mouse tissues. We found that Ang1 activated lymphatic vessel endothelial proliferation, vessel enlargement and generation of long endothelial cell filopodia that eventually fused, leading to new sprouts and vessel development. Cutaneous lymphatic hyperplasia was also detected in transgenic mice expressing Ang1 in the basal epidermal cells. Tie2 was expressed in the lymphatic endothelial cells and Ang1 stimulation of these cells resulted in upregulation of vascular endothelial growth factor receptor (VEGFR)-3. Furthermore, a soluble form of VEGFR-3 inhibited the observed lymphatic sprouting. Our results reinforce the concept that Ang1 therapy may be useful in settings of tissue edema. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Angiopoietins meet lymphatics Hellmut G. Augustin Blood 2005 105: 4541-4542. [Full Text] [PDF] This article has been cited by other articles: Autocrine Loop between Vascular Endothelial Growth Factor (VEGF)-C and VEGF Receptor-3 Positively Regulates Tumor-Associated Lymphangiogenesis in Oral Squamoid Cancer Cells Am. J. Pathol., October 1, 2009; 175(4): 1709 - 1721. T. Holopainen, H. Huang, C. Chen, K. E. Kim, L. Zhang, F. Zhou, W. Han, C. Li, J. Yu, J. Wu, et al. Angiopoietin-1 Overexpression Modulates Vascular Endothelium to Facilitate Tumor Cell Dissemination and Metastasis Establishment Cancer Res., June 1, 2009; 69(11): 4656 - 4664. [Abstract] [Full Text] [PDF] C. Norrmen, K. I. Ivanov, J. Cheng, N. Zangger, M. Delorenzi, M. Jaquet, N. Miura, P. Puolakkainen, V. Horsley, J. Hu, et al. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1 J. Cell Biol., May 4, 2009; 185(3): 439 - 457. [Abstract] [Full Text] [PDF] J. Lahdenranta, J. Hagendoorn, T. P. Padera, T. Hoshida, G. Nelson, S. Kashiwagi, R. K. Jain, and D. Fukumura Endothelial Nitric Oxide Synthase Mediates Lymphangiogenesis and Lymphatic Metastasis Cancer Res., April 1, 2009; 69(7): 2801 - 2808. [Abstract] [Full Text] [PDF] J. W. Shin, R. Huggenberger, and M. Detmar Transcriptional profiling of VEGF-A and VEGF-C target genes in lymphatic endothelium reveals endothelial-specific molecule-1 as a novel mediator of lymphangiogenesis Blood, September 15, 2008; 112(6): 2318 - 2326. [Abstract] [Full Text] [PDF] C. A. Heckman, T. Holopainen, M. Wirzenius, S. Keskitalo, M. Jeltsch, S. Yla-Herttuala, S. R. Wedge, J. M. Jurgensmeier, and K. Alitalo The Tyrosine Kinase Inhibitor Cediranib Blocks Ligand-Induced Vascular Endothelial Growth Factor Receptor-3 Activity and Lymphangiogenesis Cancer Res., June 15, 2008; 68(12): 4754 - 4762. [Abstract] [Full Text] [PDF] M. Oka, C. Iwata, H. I. Suzuki, K. Kiyono, Y. Morishita, T. Watabe, A. Komuro, M. R. Kano, and K. Miyazono Inhibition of endogenous TGF-{beta} signaling enhances lymphangiogenesis Blood, May 1, 2008; 111(9): 4571 - 4579. [Abstract] [Full Text] [PDF] R. S. Srinivasan, M. E. Dillard, O. V. Lagutin, F.-J. Lin, S. Tsai, M.-J. Tsai, I. M. Samokhvalov, and G. Oliver Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature Genes & Dev., October 1, 2007; 21(19): 2422 - 2432. [Abstract] [Full Text] [PDF] S. S. Sundar and T. S. Ganesan Role of Lymphangiogenesis in Cancer J. Clin. Oncol., September 20, 2007; 25(27): 4298 - 4307. [Abstract] [Full Text] [PDF] M. Wirzenius, T. Tammela, M. Uutela, Y. He, T. Odorisio, G. Zambruno, J. A. Nagy, H. F. Dvorak, S. Yla-Herttuala, M. Shibuya, et al. Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting J. Exp. Med., June 11, 2007; 204(6): 1431 - 1440. [Abstract] [Full Text] [PDF] T. Tammela, Y. He, J. Lyytikka, M. Jeltsch, J. Markkanen, K. Pajusola, S. Yla-Herttuala, and K. Alitalo Distinct Architecture of Lymphatic Vessels Induced by Chimeric Vascular Endothelial Growth Factor-C/Vascular Endothelial Growth Factor Heparin-Binding Domain Fusion Proteins Circ. Res., May 25, 2007; 100(10): 1468 - 1475. [Abstract] [Full Text] [PDF] J. 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[Abstract] [Full Text] [PDF] N. P.J. Brindle, P. Saharinen, and K. Alitalo Signaling and Functions of Angiopoietin-1 in Vascular Protection Circ. Res., April 28, 2006; 98(8): 1014 - 1023. [Abstract] [Full Text] [PDF] T. Morisada, Y. Oike, Y. Yamada, T. Urano, M. Akao, Y. Kubota, H. Maekawa, Y. Kimura, M. Ohmura, T. Miyamoto, et al. Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation Blood, June 15, 2005; 105(12): 4649 - 4656. [Abstract] [Full Text] [PDF]

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