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A feature that makes cancer particularly deadly is its ability to spread throughout the body via the blood or the lymph vessels. This spreading is called metastasis, and understanding and combating this process would be a major breakthrough in cancer treatment.
Cancerous tissue is known to contain a high concentration of new blood vessels, formed by a process known as angiogenesis. A less well-understood element of cancerous tissue is its high density of new lymph vessels, formed by lymphangiogenesis. Three papers in the February issue of (Nature Medicine Vol. 7, No. 2, 01 Feb 2001) clarify the process underlying lymphangiogenesis and suggest potential therapies for its treatment. Both angiogenesis and lymphangiogenesis occur through the same family of receptors called vascular endothelial growth factors receptors (VEGFR). New blood vessels are formed through stimulation of the VEGFR-2 and new lymph vessels through the VEGFR-3. Steven Stacker and colleagues at the Ludwig Institute for Cancer Research, Australia, used a mouse model to demonstrate that a molecule that attaches to the VEGFR-3 called VEGF-D, causes the formation of both blood and lymph vessels within tumors. It also led to spread of cancerous cells to lymph nodes, an effect that was blocked with an antibody to VEGF-D. Meanwhile, Michael Detmar and colleagues at Massachusetts General Hospital, Boston, transplanted human breast tumors into mice and found that another molecule, which also attaches to VEGFR-3, VEGF-C, caused the growth of lymph vessels within the tumors and metastasis to the lymph nodes and lungs. VEGF-C is overexpressed in human breast cancer cells. Again, using a mouse model, Kari Alitalo and colleagues of the University of Helsinki, Finland, showed that a soluble form of the VEGFR-3 can block the actions of both VEGF-C and VEGF-D. When expressed in transgenic mice, soluble VEGFR-3 prevented the formation of lymph vessels and caused already formed lymph vessels to regress. The results suggest that this might form the basis of a treatment for human lymphedema, a chronic swelling of limbs due to dysfunction of the lymphatic vessels that is often caused by a mutation of the VEGFR-3 gene. The interplay between the VEGF molecules and receptors and their effects on lymph and blood vessel formation and tumor metastasis is explained in a News & Views written article by Karl Plate of the FAU Erlangen-Nurnberg, Germany. Dr. Kari Alitalo
Molecular/Cancer Biology Laboratory
Haartman Institute
University of Helsinki
Helsinki, Finland
Tel: +358 9 1912 6434
Fax: +358 9 1912 6448
Email: Kari.Alitalo@Helsinki.Fi
Dr. Michael Detmar
CBRC/Dept. of Dermatology
Massachusetts General Hospital
Building 149, 13th Street
Charlestown, MA 02129
Tel: +1 617 724 1170
Fax: +1 617 726 4453
Email: michael.detmar@cbrc2.mgh.harvard.edu
Dr. Steven A. Stacker
Ludwig Institute for Cancer Research
Post Office Box 2008
Royal Melbourne Hospital
Victoria 3050, Australia
Tel: +61-3-9341-3155
Fax: +61-3-9341-3104
Email: steven.stacker@ludwig.edu.au
Dr Karl H. Plate FAU Erlangen-Nürnberg
Department of Neuropathology
Krankenhausstr. 8-10
D-91054 Erlangen
Germany
Tel: +49 761 270 5106
Fax: +49 761 270 5050
Email: plate@rzmail.uni-erlangen.de
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza
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