Lymphangiogenesis and lymphatic vessel remodelling in cancer

The lymphatic vasculature is essential for immune function, tissue fluid homeostasis and the absorption of dietary fat.The process of lymphangiogenesis involves the formation of new lymphatic vessels from pre-existing lymphatics; this occurs during embryonic development, wound healing and in various pathological contexts, including cancer.Tumour cells and cells of the tumour microenvironment produce growth factors that promote lymphangiogenesis from initial lymphatics, as well as the enlargement of initial and collecting lymphatic vessels in and around solid tumours. The enlargement of collecting lymphatics can involve remodelling of these vessels by smooth muscle cells.Lymphangiogenic factors (such as vascular endothelial growth factor C (VEGFC) and VEGFD) can induce the metastatic spread of tumours in mouse models of cancer.Clinicopathological studies have shown that the production of lymphangiogenic factors, lymphangiogenesis and lymphatic remodelling can correlate with cancer progression.Lymphatic vessels provide a therapeutic target for modulating the immune response to cancer and restricting metastasis; clinical trials of agents that target lymphangiogenic signalling pathways are underway.Mouse models and genome-wide functional screening approaches might identify further important signalling pathways in tumour lymphangiogenesis that could be potential diagnostic and therapeutic targets.