help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Paavonen, K.
Right arrow Articles by Alitalo, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Paavonen, K.
Right arrow Articles by Alitalo, K.
(American Journal of Pathology. 2000;156:1499-1504.)
© 2000 American Society for Investigative Pathology

Short Communications

Vascular Endothelial Growth Factor Receptor-3 in Lymphangiogenesis in Wound Healing

Karri Paavonen*, Pauli Puolakkainen{dagger}, Lotta Jussila*, Tiina Jahkola{ddagger} and Kari Alitalo*

From the Molecular/Cancer Biology Laboratory,*
Haartman Institute, University of Helsinki, Helsinki; and the Departments of Surgery{dagger}
and Plastic Surgery,{ddagger}
Helsinki University Central Hospital, Helsinki, Finland

Vascular endothelial growth factor receptor-3 (VEGFR-3) is essential for embryonic cardiovascular development, but thereafter becomes confined to the lymphatic endothelium in adult tissues. We have here studied VEGFR-3 expression in experimental wounds of pigs and chronic inflammatory wounds of humans. In healing incisional and punch biopsy wounds made in the dorsal skin of pigs, angiogenic blood vessels, identified by use of the blood vascular endothelial markers vWF and PAL-E and the basal lamina protein laminin, developed into the granulation tissue stroma from day 4 onward, being most abundant on days 5 and 6 and regressing thereafter. VEGFR-3-positive vessels were observed in the granulation tissue from day 5 onward. These vessels were distinct from the PAL-E/laminin/vWF-positive vessels and fewer in number, and they appeared to sprout from pre-existing VEGFR-3-positive lymphatic vessels at the wound edge. Unlike the blood vessels, very few VEGFR-3-positive lymphatic vessels persisted on day 9 and none on day 14. In chronic wounds such as ulcers and decubitus wounds of the lower extremity of humans, VEGFR-3 was also weakly expressed in the vascular endothelium. Our results suggest that transient lymphangiogenesis occurs in parallel with angiogenesis in healing wounds and that VEGFR-3 becomes up-regulated in blood vessel endothelium in chronic inflammatory wounds.




This article has been cited by other articles:


Home page
 Ann. N. Y. Acad. Sci.Home page
W. S. SHIN and S. G. ROCKSON
Animal Models for the Molecular and Mechanistic Study of Lymphatic Biology and Disease
Ann. N.Y. Acad. Sci., May 1, 2008; 1131(1): 50 - 74.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
T. TERVALA, E. SUOMINEN, and A. SAARISTO
Targeted Treatment for Lymphedema and Lymphatic Metastasis
Ann. N.Y. Acad. Sci., May 1, 2008; 1131(1): 215 - 224.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Donnem, S. Al-Saad, K. Al-Shibli, M. P. Delghandi, M. Persson, M. N. Nilsen, L.-T. Busund, and R. M. Bremnes
Inverse Prognostic Impact of Angiogenic Marker Expression in Tumor Cells versus Stromal Cells in Non Small Cell Lung Cancer
Clin. Cancer Res., November 15, 2007; 13(22): 6649 - 6657.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. E. Jaalouk, M. G. Ozawa, J. Sun, J. Lahdenranta, R. O. Schlingemann, R. Pasqualini, and W. Arap
The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor Binding Site within Neuropilin-1
Cancer Res., October 15, 2007; 67(20): 9623 - 9629.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
C. Gridelli, P. Maione, A. Rossi, and F. De Marinis
The Role of Bevacizumab in the Treatment of Non-Small Cell Lung Cancer: Current Indications and Future Developments
Oncologist, October 1, 2007; 12(10): 1183 - 1193.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. A.H. Jarvinen and E. Ruoslahti
Molecular Changes in the Vasculature of Injured Tissues
Am. J. Pathol., August 1, 2007; 171(2): 702 - 711.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Eichten, W. C. Hyun, and L. M. Coussens
Distinctive Features of Angiogenesis and Lymphangiogenesis Determine Their Functionality during De novo Tumor Development
Cancer Res., June 1, 2007; 67(11): 5211 - 5220.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. E. Tobler and M. Detmar
Tumor and lymph node lymphangiogenesis--impact on cancer metastasis
J. Leukoc. Biol., October 1, 2006; 80(4): 691 - 696.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
A. Saaristo, T. Tammela, A. Farkkila, M. Karkkainen, E. Suominen, S. Yla-Herttuala, and K. Alitalo
Vascular Endothelial Growth Factor-C Accelerates Diabetic Wound Healing
Am. J. Pathol., September 1, 2006; 169(3): 1080 - 1087.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
A. Morabito, E. De Maio, M. Di Maio, N. Normanno, and F. Perrone
Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors in Clinical Trials: Current Status and Future Directions
Oncologist, July 1, 2006; 11(7): 753 - 764.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Amino, Y. Ideyama, M. Yamano, S. Kuromitsu, K. Tajinda, K. Samizu, H. Hisamichi, A. Matsuhisa, K. Shirasuna, M. Kudoh, et al.
YM-359445, an Orally Bioavailable Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor, Has Highly Potent Antitumor Activity against Established Tumors
Clin. Cancer Res., March 1, 2006; 12(5): 1630 - 1638.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Juttner, C. Wissmann, T. Jons, M. Vieth, J. Hertel, S. Gretschel, P. M. Schlag, W. Kemmner, and M. Hocker
Vascular Endothelial Growth Factor-D and Its Receptor VEGFR-3: Two Novel Independent Prognostic Markers in Gastric Adenocarcinoma
J. Clin. Oncol., January 10, 2006; 24(2): 228 - 240.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. He, I. Rajantie, K. Pajusola, M. Jeltsch, T. Holopainen, S. Yla-Herttuala, T. Harding, K. Jooss, T. Takahashi, and K. Alitalo
Vascular Endothelial Cell Growth Factor Receptor 3-Mediated Activation of Lymphatic Endothelium Is Crucial for Tumor Cell Entry and Spread via Lymphatic Vessels
Cancer Res., June 1, 2005; 65(11): 4739 - 4746.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Cursiefen, S. Ikeda, P. M. Nishina, R. S. Smith, A. Ikeda, D. Jackson, J.-S. Mo, L. Chen, M. R. Dana, B. Pytowski, et al.
Spontaneous Corneal Hem- and Lymphangiogenesis in Mice with Destrin-Mutation Depend on VEGFR3 Signaling
Am. J. Pathol., May 1, 2005; 166(5): 1367 - 1377.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. J. Hicklin and L. M. Ellis
Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis
J. Clin. Oncol., February 10, 2005; 23(5): 1011 - 1027.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
M I Koukourakis, A Giatromanolaki, E Sivridis, C Simopoulos, K C Gatter, A L Harris, and D G Jackson
LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer
J. Clin. Pathol., February 1, 2005; 58(2): 202 - 206.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
Y. Aoki and G. Tosato
Lymphatic Regeneration: New Insights From VEGFR-3 Blockade
J Natl Cancer Inst, January 5, 2005; 97(1): 2 - 3.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Groger, R. Loewe, W. Holnthoner, R. Embacher, M. Pillinger, G. S. Herron, K. Wolff, and P. Petzelbauer
IL-3 Induces Expression of Lymphatic Markers Prox-1 and Podoplanin in Human Endothelial Cells
J. Immunol., December 15, 2004; 173(12): 7161 - 7169.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn
Vascular Endothelial Growth Factor and Angiogenesis
Pharmacol. Rev., December 1, 2004; 56(4): 549 - 580.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
I. NILSSON, C. ROLNY, Y. WU, B. PYTOWSKI, D. HICKLIN, K. ALITALO, L. CLAESSON-WELSH, and S. WENNSTROM
Vascular endothelial growth factor receptor-3 in hypoxia-induced vascular development
FASEB J, October 1, 2004; 18(13): 1507 - 1515.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. K. Chang, G. Garcia-Cardena, F. Farnebo, M. Fannon, E. J. Chen, C. Butterfield, M. A. Moses, R. C. Mulligan, J. Folkman, and A. Kaipainen
Dose-dependent response of FGF-2 for lymphangiogenesis
PNAS, August 10, 2004; 101(32): 11658 - 11663.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
P. SAHARINEN and T. V. PETROVA
Molecular Regulation of Lymphangiogenesis
Ann. N.Y. Acad. Sci., April 1, 2004; 1014(1): 76 - 87.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
B. K. McColl, M. E. Baldwin, S. Roufail, C. Freeman, R. L. Moritz, R. J. Simpson, K. Alitalo, S. A. Stacker, and M. G. Achen
Plasmin Activates the Lymphangiogenic Growth Factors VEGF-C and VEGF-D
J. Exp. Med., September 15, 2003; 198(6): 863 - 868.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
O. Stoeltzing, W. Liu, N. Reinmuth, A. Parikh, S. A. Ahmad, Y. D. Jung, F. Fan, and L. M. Ellis
Angiogenesis and Antiangiogenic Therapy of Colon Cancer Liver Metastasis
Ann. Surg. Oncol., August 1, 2003; 10(7): 722 - 733.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. WERNER and R. GROSE
Regulation of Wound Healing by Growth Factors and Cytokines
Physiol Rev, July 1, 2003; 83(3): 835 - 870.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. C. Boardman and M. A. Swartz
Interstitial Flow as a Guide for Lymphangiogenesis
Circ. Res., April 18, 2003; 92(7): 801 - 808.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Hirakawa, Y.-K. Hong, N. Harvey, V. Schacht, K. Matsuda, T. Libermann, and M. Detmar
Identification of Vascular Lineage-Specific Genes by Transcriptional Profiling of Isolated Blood Vascular and Lymphatic Endothelial Cells
Am. J. Pathol., February 1, 2003; 162(2): 575 - 586.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. Salven, S. Mustjoki, R. Alitalo, K. Alitalo, and S. Rafii
VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells
Blood, January 1, 2003; 101(1): 168 - 172.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
C. Cursiefen, U. Schlotzer-Schrehardt, M. Kuchle, L. Sorokin, S. Breiteneder-Geleff, K. Alitalo, and D. Jackson
Lymphatic Vessels in Vascularized Human Corneas: Immunohistochemical Investigation Using LYVE-1 and Podoplanin
Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2127 - 2135.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. A. STACKER, M. E. BALDWIN, and M. G. ACHEN
The role of tumor lymphangiogenesis in metastatic spread
FASEB J, July 1, 2002; 16(9): 922 - 934.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
L. Jussila and K. Alitalo
Vascular Growth Factors and Lymphangiogenesis
Physiol Rev, July 1, 2002; 82(3): 673 - 700.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Kubo, R. Cao, E. Brakenhielm, T. Makinen, Y. Cao, and K. Alitalo
Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea
PNAS, June 25, 2002; 99(13): 8868 - 8873.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. V. Byzova, C. K. Goldman, J. Jankau, J. Chen, G. Cabrera, M. G. Achen, S. A. Stacker, K. A. Carnevale, M. Siemionow, S. R. Deitcher, et al.
Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo
Blood, May 29, 2002; 99(12): 4434 - 4442.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
G. Oliver and M. Detmar
The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature
Genes & Dev., April 1, 2002; 16(7): 773 - 783.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. D. White, P. W. Hewett, D. Kosuge, T. McCulloch, B. C. Enholm, J. Carmichael, and J. C. Murray
Vascular Endothelial Growth Factor-D Expression Is an Independent Prognostic Marker for Survival in Colorectal Carcinoma
Cancer Res., March 1, 2002; 62(6): 1669 - 1675.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. F. Wang, X.-F. Zhang, and J. E. Groopman
Stimulation of beta 1 Integrin Induces Tyrosine Phosphorylation of Vascular Endothelial Growth Factor Receptor-3 and Modulates Cell Migration
J. Biol. Chem., November 2, 2001; 276(45): 41950 - 41957.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. Clarijs, L. Schalkwijk, D. J. Ruiter, and R. M. W. de Waal
Lack of Lymphangiogenesis Despite Coexpression of VEGF-C and Its Receptor Flt-4 in Uveal Melanoma
Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1422 - 1428.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
M. S. Pepper
Lymphangiogenesis and Tumor Metastasis: Myth or Reality?
Clin. Cancer Res., March 1, 2001; 7(3): 462 - 468.
[Abstract] [Full Text]

Home page
 Am. J. Pathol.Home page
R. J. B. Nibbs, E. Kriehuber, P. D. Ponath, D. Parent, S. Qin, J. D. M. Campbell, A. Henderson, D. Kerjaschki, D. Maurer, G. J. Graham, et al.
The {beta}-Chemokine Receptor D6 Is Expressed by Lymphatic Endothelium and a Subset of Vascular Tumors
Am. J. Pathol., March 1, 2001; 158(3): 867 - 877.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. E. Baldwin, B. Catimel, E. C. Nice, S. Roufail, N. E. Hall, K. L. Stenvers, M. J. Karkkainen, K. Alitalo, S. A. Stacker, and M. G. Achen
The Specificity of Receptor Binding by Vascular Endothelial Growth Factor-D Is Different in Mouse and Man
J. Biol. Chem., May 25, 2001; 276(22): 19166 - 19171.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the American Society for Investigative Pathology.