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Role of Lymphangiogenesis in Cancer

Sudha S. Sundar, Trivadi S. Ganesan

From the Department of Gynaecological Oncology, Cheltenham General Hospital, Gloucestershire Hospitals Foundation Trust, Gloucestershire, United Kingdom; and Cancer Institute and Institute of Molecular Medicine, Amrita Institute of Medical Sciences, Kerala, India

Address reprint requests to Sudha S. Sundar, MPhil, MRCOG, Cheltenham General Hospital, 9 Northcroft, The Park, Cheltenham, Gloucestershire GL50 2NL, United Kingdom; e-mail: sudhasundar{at}minox.demon.co.uk

Regional lymph node metastasis is a common event in solid tumors and is considered a marker for dissemination, increased stage, and worse prognosis. Despite rapid advances in tumor biology, the molecular processes that underpin lymphatic invasion and lymph node metastasis remain poorly understood. However, exciting discoveries have been made in the field of lymphangiogenesis in recent years. The identification of vascular endothelial growth factor ligands and cognate receptors involved in lymphangiogenesis, an understanding of the embryology of the mammalian lymphatic system, the recent isolation of pure populations of lymphatic endothelial cells, the investigation of lymphatic metastases in animal models, and the identification of markers that discriminate lymphatics from blood vessels at immunohistochemistry are current advances in the field of lymphangiogenesis, and as such are the main focus of this article. This review also evaluates evidence for lymphangiogenesis (ie, new lymphatic vessel formation in cancer) and critically reviews current data on the prognostic significance of lymphatic vascular density in tumors. A targeted approach to block pathways of lymphangiogenesis seems to be an attractive anticancer treatment strategy. Conversely, promotion of lymphangiogenesis may be a promising approach to the management of treatment-induced lymphedema in cancer survivors. Finally, the implications of these developments in cancer therapeutics and directions for future research are discussed.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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