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Molecular/Cancer Biology Laboratory and Department of Pathology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland;
Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000, USA; and
Angiogenesis Laboratory, Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Parkville, Victoria, Australia
2Correspondence: Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute, Haartmaninkatu 3, University of Helsinki, 00014 Helsinki, Finland. E-mail: Kari.Alitalo{at}Helsinki.fi
Recently, vascular endothelial growth factor receptor 3 (VEGFR-3) has
been shown to provide a specific marker for lymphatic endothelia in
certain human tissues. In this study, we have investigated the
expression of VEGFR-3 and its ligands VEGF-C and VEGF-D in fetal and
adult tissues. VEGFR-3 was consistently detected in the endothelium of
lymphatic vessels such as the thoracic duct, but fenestrated
capillaries of several organs including the bone marrow, splenic and
hepatic sinusoids, kidney glomeruli and endocrine glands also expressed
this receptor. VEGF-C and VEGF-D, which bind both VEGFR-2 and VEGFR-3
were expressed in vascular smooth muscle cells. In addition, intense
cytoplasmic staining for VEGF-C was observed in neuroendocrine cells
such as the 
cells of the islets of Langerhans, prolactin secreting
cells of the anterior pituitary, adrenal medullary cells, and dispersed
neuroendocrine cells of the gastrointestinal tract. VEGF-D was observed
in the innermost zone of the adrenal cortex and in certain dispersed
neuroendocrine cells. These results suggest that VEGF-C and VEGF-D have
a paracrine function and perhaps a role in peptide release from
secretory granules of certain neuroendocrine cells to surrounding
capillaries.—Partanen, T. A., Arola, J., Saaristo, A., Jussila,
L., Ora, A., Miettinen, M., Stacker, S. A., Achen, M. G.,
Alitalo, K. VEGF-C and VEGF-D expression in neuroendocrine cells and
their receptor, VEGFR-3, in fenestrated blood vessels in human tissues.
Key Words: growth substance • receptor tyrosine kinase • vascular endothelium
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M. J. Karkkainen, A. Saaristo, L. Jussila, K. A. Karila, E. C. Lawrence, K. Pajusola, H. Bueler, A. Eichmann, R. Kauppinen, M. I. Kettunen, et al. A model for gene therapy of human hereditary lymphedema PNAS, October 5, 2001; (2001) 221449198. [Abstract] [Full Text] [PDF]
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E. Kriehuber, S. Breiteneder-Geleff, M. Groeger, A. Soleiman, S. F. Schoppmann, G. Stingl, D. Kerjaschki, and D. Maurer Isolation and Characterization of Dermal Lymphatic and Blood Endothelial Cells Reveal Stable and Functionally Specialized Cell Lineages J. Exp. Med., September 17, 2001; 194(6): 797 - 808. [Abstract] [Full Text] [PDF]
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B. Enholm, T. Karpanen, M. Jeltsch, H. Kubo, F. Stenback, R. Prevo, D. G. Jackson, S. Yla-Herttuala, and K. Alitalo Adenoviral Expression of Vascular Endothelial Growth Factor-C Induces Lymphangiogenesis in the Skin Circ. Res., March 30, 2001; 88(6): 623 - 629. [Abstract] [Full Text] [PDF]
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M. J. Karkkainen, A. Saaristo, L. Jussila, K. A. Karila, E. C. Lawrence, K. Pajusola, H. Bueler, A. Eichmann, R. Kauppinen, M. I. Kettunen, et al. A model for gene therapy of human hereditary lymphedema PNAS, October 23, 2001; 98(22): 12677 - 12682. [Abstract] [Full Text] [PDF]
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