help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karpanen, T.
Right arrow Articles by Alitalo, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karpanen, T.
Right arrow Articles by Alitalo, K.
(American Journal of Pathology. 2006;169:708-718.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.051200

Lymphangiogenic Growth Factor Responsiveness Is Modulated by Postnatal Lymphatic Vessel Maturation

Terhi Karpanen*, Maria Wirzenius*, Taija Mäkinen*, Tanja Veikkola*, Hidde J. Haisma{dagger}, Marc G. Achen{ddagger}, Steven A. Stacker{ddagger}, Bronislaw Pytowski§, Seppo Ylä-Herttuala{dagger} and Kari Alitalo*

From the Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research,* Biomedicum Helsinki and Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland; the Department of Therapeutic Gene Modulation,{dagger} University of Groningen, Groningen, The Netherlands; the Ludwig Institute for Cancer Research,{ddagger} Royal Melbourne Hospital, Victoria, Australia; and Molecular and Cellular Biology,§ ImClone Systems, New York, New York

Lymphatic vessel plasticity and stability are of considerable importance when attempting to treat diseases associated with the lymphatic vasculature. Development of lymphatic vessels during embryogenesis is dependent on vascular endothelial growth factor (VEGF)-C but not VEGF-D. Using a recombinant adenovirus encoding a soluble form of their receptor VEGFR-3 (AdVEGFR-3-Ig), we studied lymphatic vessel dependency on VEGF-C and VEGF-D induced VEGFR-3 signaling in postnatal and adult mice. Transduction with AdVEGFR-3-Ig led to regression of lymphatic capillaries and medium-sized lymphatic vessels in mice under 2 weeks of age without affecting collecting lymphatic vessels or the blood vasculature. No effect was observed after this period. The lymphatic capillaries of neonatal mice also regressed partially in response to recombinant VEGFR-3-Ig or blocking antibodies against VEGFR-3, but not to adenovirus-encoded VEGFR-2-Ig. Despite sustained inhibitory VEGFR-3-Ig levels, lymphatic vessel regrowth was observed at 4 weeks of age. Interestingly, whereas transgenic expression of VEGF-C in the skin induced lymphatic hyperplasia even during embryogenesis, similar expression of VEGF-D resulted in lymphangiogenesis predominantly after birth. These results indicate considerable plasticity of lymphatic vessels during the early postnatal period but not thereafter, suggesting that anti-lymphangiogenic therapy can be safely applied in adults.




This article has been cited by other articles:


Home page
 FASEB J.Home page
F. Bruyere and A. Noel
Lymphangiogenesis: in vitro and in vivo models
FASEB J, January 1, 2010; 24(1): 8 - 21.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. Birke, E. Lutjen-Drecoll, D. Kerjaschki, and M. T. Birke
Expression of Podoplanin and Other Lymphatic Markers in the Human Anterior Eye Segment
Invest. Ophthalmol. Vis. Sci., January 1, 2010; 51(1): 344 - 354.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. Schomber, A. Zumsteg, K. Strittmatter, I. Crnic, H. Antoniadis, A. Littlewood-Evans, J. Wood, and G. Christofori
Differential effects of the vascular endothelial growth factor receptor inhibitor PTK787/ZK222584 on tumor angiogenesis and tumor lymphangiogenesis
Mol. Cancer Ther., January 1, 2009; 8(1): 55 - 63.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
N. C. Johnson, M. E. Dillard, P. Baluk, D. M. McDonald, N. L. Harvey, S. L. Frase, and G. Oliver
Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity
Genes & Dev., December 1, 2008; 22(23): 3282 - 3291.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Lohela, H. Helotera, P. Haiko, D. J. Dumont, and K. Alitalo
Transgenic Induction of Vascular Endothelial Growth Factor-C Is Strongly Angiogenic in Mouse Embryos but Leads to Persistent Lymphatic Hyperplasia in Adult Tissues
Am. J. Pathol., December 1, 2008; 173(6): 1891 - 1901.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Clasper, D. Royston, D. Baban, Y. Cao, S. Ewers, S. Butz, D. Vestweber, and D. G. Jackson
A Novel Gene Expression Profile in Lymphatics Associated with Tumor Growth and Nodal Metastasis
Cancer Res., September 15, 2008; 68(18): 7293 - 7303.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. Haiko, T. Makinen, S. Keskitalo, J. Taipale, M. J. Karkkainen, M. E. Baldwin, S. A. Stacker, M. G. Achen, and K. Alitalo
Deletion of Vascular Endothelial Growth Factor C (VEGF-C) and VEGF-D Is Not Equivalent to VEGF Receptor 3 Deletion in Mouse Embryos
Mol. Cell. Biol., August 1, 2008; 28(15): 4843 - 4850.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Uzarski, M. B. Drelles, S. E. Gibbs, E. L. Ongstad, J. C. Goral, K. K. McKeown, A. M. Raehl, M. A. Roberts, B. Pytowski, M. R. Smith, et al.
The resolution of lymphedema by interstitial flow in the mouse tail skin
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1326 - H1334.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Jackowski, M. Janusch, E. Fiedler, W. C. Marsch, E. J. Ulbrich, G. Gaisbauer, J. Dunst, D. Kerjaschki, and P. Helmbold
Radiogenic Lymphangiogenesis in the Skin
Am. J. Pathol., July 1, 2007; 171(1): 338 - 348.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
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]

Home page
 FASEB J.Home page
B. K. McColl, K. Paavonen, T. Karnezis, N. C. Harris, N. Davydova, J. Rothacker, E. C. Nice, K. W. Harder, S. Roufail, M. L. Hibbs, et al.
Proprotein convertases promote processing of VEGF-D, a critical step for binding the angiogenic receptor VEGFR-2
FASEB J, April 1, 2007; 21(4): 1088 - 1098.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Laakkonen, M. Waltari, T. Holopainen, T. Takahashi, B. Pytowski, P. Steiner, D. Hicklin, K. Persaud, J. R. Tonra, L. Witte, et al.
Vascular Endothelial Growth Factor Receptor 3 Is Involved in Tumor Angiogenesis and Growth
Cancer Res., January 15, 2007; 67(2): 593 - 599.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. L. Iruela-Arispe
When It Comes to Blocking Lymphatics, It Is All a Question of Time
Am. J. Pathol., August 1, 2006; 169(2): 347 - 350.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.