Lymphangiogenesis and breast cancer metastasis.

Breast cancer is one of the commonest malignancies in women in the western world. It spreads predominantly via the lymphatic system. However, the understanding of the formation of lymphatics, lymphangiogenesis, has been limited. This has been largely due to the previous lack of lymphatic specific markers. The most specific marker used in humans has been the vascular endothelial growth factor receptor 3 (VEGFR-3). However, this is also found on blood vessel endothelium. The other vascular endothelial factor receptors (VEGFR-1 and -2) are primarily blood vessel receptors. More recently, novel, specific markers for lymphatics have been discovered, such as LYVE-1, prox I and podoplanin, enabling further research into this new field. Each of these new markers is described in detail. The article also outlines the current understanding in breast cancer metastasis, with an emphasis on the more recent research into lymphangiogenesis. Since these specific markers are now available, quantitation of lymphangiogenesis is now possible by using either immunohistochemistry or quantitative PCR approaches. In addition, to breast cancer, research into many other cancers is now possible using these methods and new markers. With this in mind, possible therapeutic strategies for the future are discussed.