Lymphangiogenesis Signalling Pathways in Human Disease

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Current Strategies for Modulating Lymphangiogenesis Signalling Pathways in Human Disease

Authors: Stacker, S. A.1; Hughes, R. A.1; Williams, R. A.1; Achen, M.
G.1

Source: Current Medicinal Chemistry, Volume 13, Number 7, March 2006,
pp. 783-792(10)

Publisher: Bentham Science Publishers

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

Document Type: Research article

Affiliations: 1: Angiogenesis Laboratory, Ludwig Institute for Cancer
Research, PO Box 2008, Royal Melbourne Hospital, Victoria 3050,
Australia.

http://www.ingentaconnect.com/content/b ... 50762f425a

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