Lymphangiogenesis in human gynaecological cancers.

The metastatic spread of tumor cells is responsible for the majority of cancer deaths, and with few exceptions, all cancers can metastasize. Clinical findings have for a long time suggested that by providing a pathway for tumor cell dissemination, tumor-associated lymphatics act as key components of metastatic spread. This is believed to occur principally via pre-existing and possibly also newly formed lymphatics (lymphangiogenesis). Increased expression of vascular endothelial growth factor-C (VEGF-C) and VEGF-D in primary tumors correlates with increased dissemination of tumor cells to regional lymph nodes (LNs) in a variety of human carcinomas. Here we will review the mechanisms of lymphangiogenesis, particularly in the context of metastatic tumor spread, and will critically examine the role of VEGF-C and VEGF-D in this process in gynaecological cancers. Potential anti-lymphangiogenic strategies are also discussed.