Abstract
The recent discovery that members of the vascular endothelial growth factor (VEGF) family of secreted glycoproteins can mediate lymphatic vessel growth (lymphangiogenesis) via cell surface receptor tyrosine kinases expressed on endothelial cells has opened the way for therapeutic intervention for pathologies involving dysregulated lymphatic vessel function. At least two members of this family, VEGF-C and VEGF-D, have been shown to induce lymphangiogenesis in vivo. Lymphatic vessels and their specific growth factors have been directly implicated in a number of significant human pathologies. In cancer, VEGF-C and VEGF-D appear to correlate with tumor metastasis and poor patient outcome in a range of prevalent human cancers. Experimental studies have demonstrated that expression of the lymphangiogenic growth factors in tumor models induces increased lymphangiogenesis and results in spread of tumor cells via the lymphatics. In contrast, conditions such as lymphedema, where lymphatic vessels fail to clear fluid from interstitial spaces, are opportunities for which the application of growth factors to generate new lymphatic vessels may be a viable therapeutic option. The list of molecules that control lymphangiogenesis is now expanding, allowing more opportunities for the development of drugs with which to manipulate the relevant signalling pathways. Modulating these pathways and other molecules with specificity to the lymphatic endothelium could offer alternative treatments for a number of important clinical conditions.
Keywords: Lymphangiogenesis, vascular endothelial growth factors, receptors, lymphedema, metastasis, lymphatic endothelium
Current Medicinal Chemistry
Title: Current Strategies for Modulating Lymphangiogenesis Signalling Pathways in Human Disease
Volume: 13 Issue: 7
Author(s): S. A. Stacker, R. A. Hughes, R. A. Williams and M. G. Achen
Affiliation:
Keywords: Lymphangiogenesis, vascular endothelial growth factors, receptors, lymphedema, metastasis, lymphatic endothelium
Abstract: The recent discovery that members of the vascular endothelial growth factor (VEGF) family of secreted glycoproteins can mediate lymphatic vessel growth (lymphangiogenesis) via cell surface receptor tyrosine kinases expressed on endothelial cells has opened the way for therapeutic intervention for pathologies involving dysregulated lymphatic vessel function. At least two members of this family, VEGF-C and VEGF-D, have been shown to induce lymphangiogenesis in vivo. Lymphatic vessels and their specific growth factors have been directly implicated in a number of significant human pathologies. In cancer, VEGF-C and VEGF-D appear to correlate with tumor metastasis and poor patient outcome in a range of prevalent human cancers. Experimental studies have demonstrated that expression of the lymphangiogenic growth factors in tumor models induces increased lymphangiogenesis and results in spread of tumor cells via the lymphatics. In contrast, conditions such as lymphedema, where lymphatic vessels fail to clear fluid from interstitial spaces, are opportunities for which the application of growth factors to generate new lymphatic vessels may be a viable therapeutic option. The list of molecules that control lymphangiogenesis is now expanding, allowing more opportunities for the development of drugs with which to manipulate the relevant signalling pathways. Modulating these pathways and other molecules with specificity to the lymphatic endothelium could offer alternative treatments for a number of important clinical conditions.
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Cite this article as:
Stacker A. S., Hughes A. R., Williams A. R. and Achen G. M., Current Strategies for Modulating Lymphangiogenesis Signalling Pathways in Human Disease, Current Medicinal Chemistry 2006; 13 (7) . https://dx.doi.org/10.2174/092986706776055625
DOI https://dx.doi.org/10.2174/092986706776055625 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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