VEGF induces lymph vessel enlargement (top) but not the sprouting of new vessels (bottom).

Lymph vessels are a follow-up act to blood vessels during embryogenesis. Vascular endothelial growth factor (VEGF) induces new blood vessel growth by binding to its receptor VEGFR-2 on vascular endothelial cells. VEGF-C and -D then kick off lymph vessel sprouting by binding to VEGFR-3 on lymphatic endothelial cells. But studies in mice that overexpress VEGF suggest that the two signaling pathways are not completely segregated. The abnormally large lymph vessels in these mice imply that VEGF somehow controls lymph vessel enlargement as well.

The team now finds that VEGFR-2 is also expressed on lymph vessels and induces their widening. But VEGF did not start lymph vessel growth anew: the missing lymph network of mouse embryos lacking VEGF-C and -D was not rescued by VEGF.

Lymphatic enlargement during inflammation helps immune cells accumulate at the site of injury or infection. But lymph vessels that don't later slim down increase the risk of chronic inflammation. Lymph vessel expansion is also dangerous during tumor growth in lymph nodes, as enlarged vessels act as highways for metastasizing tumor cells. Current antitumor strategies that target VEGF prevent blood vessel growth and thus nutrient supply to tumors. This study suggests that anti-VEGF treatment may also prevent tumor metastasis.

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