Lymphatic Vessels as Targets of Tumor Therapy?

Recent evidence on the association of lymphangiogenic growth factors with intralymphatic growth and metastasis of cancers (1–4) has raised hopes that lymphatic vessels could be used as an additional target for tumor therapy. Cancer cells spread within the body by direct invasion to surrounding tissues, spreading to body cavities, invasion into the blood vascular system (hematogenous metastasis), as well as spread via the lymphatic system (lymphatic me-tastasis). Regional lymph node dissemination is the first step in the metastasis of several common cancers and correlates highly to the prognosis of the disease. The lymph nodes that are involved in draining tissue fluid from the tumor area are called sentinel nodes, and diagnostic measures are in place to find these nodes and to remove them in cases of suspected metastasis. However, in spite of its clinical relevance , little is known about the mechanisms leading to me-tastasis via the bloodstream or via the lymphatics. Until recently, the lymphatic vessels have received much less attention than blood vessels, despite their importance in medicine. Lymphatic vessels collect protein-rich fluid and white blood cells from the interstitial space of most tissues and transport them as a whitish opaque fluid, the lymph, into the blood circulation. Small lymphatic vessels coalesce into larger vessels, which drain the lymph through the tho-racic duct into large veins in the neck region. Lymph nodes serve as filtering stations along the lymphatic vessels and lymph movement is propelled by the contraction of smooth muscles surrounding collecting lymphatic vessels and by bodily movements, the direction of flow being secured by valves as it is in veins. The lymphatic capillaries are lined by endothelial cells, which have distinct junctions with frequent large interendothelial gaps. The lymphatic capillaries also lack a continuous basement membrane, and are devoid of pericytes. Anchoring filaments connect the abluminal surfaces of lymphatic endothelial cells to the perivascular extracellular matrix and pull to maintain vessel patency in the presence of tissue edema. The absence or obstruction of lymphatic vessels, which is usually the result of an infection, surgery, or radiotherapy and in rare cases, a genetic defect, causes accumulation of a protein-rich fluid in tissues, lymphedema. The lymphatic system is also critical in fat absorption from the gut and in immune responses. Bacteria, viruses, and other foreign materials are taken up by the lym-phatic vessels and transported to the lymph nodes, where the foreign material is presented to immune cells …