♦ See referenced article, J. Biol. Chem. 2011, 286, 14952–14962
The growth and remodeling of lymphatic vessels (lymphangiogenesis) is, much like blood vessel growth, a fundamental and dynamic cellular process. Like other activities crucial for development, poorly controlled or inappropriate vascular growth is implicated in cancer (increased lymphatic vasculature contributes to lymph node metastasis). A major player in lymphangiogenesis is the lymphatic vascular endothelial growth factor VEGF-C, which binds a receptor on the cell surface and activates a signaling pathway leading to proliferation of the vasculature. It is known that heparan sulfate, a sulfated polysaccharide, helps some growth factors bind their receptors; however, a direct role for heparan sulfate in lymphangiogenesis had not been demonstrated. In this Paper of the Week, Xin Yin, Scott Johns, and colleagues use a multipronged approach to thoroughly examine the role of heparan sulfate in VEGF-C-mediated lymphangiogenesis. They show that removing heparan sulfate, either by degrading the cell's supply or by preventing its biosynthesis, significantly reduces VEGF-C's ability to activate downstream signaling components. These findings indicate that interfering with heparan sulfate could reduce or prevent lymphangiogenesis during cancer progression and could provide a novel target for cancer therapies.
Removal of lymphatic endothelial cell-surface heparan sulfate inhibits signaling in response to VEGF-C.