Lymphangiogenesis and tumour metastasis.

The lymphatic system serves to collect and transport interstitial fluid (lymph) within tissues, and plays an important role in the immune response. The lymphatic system also constitutes one of most important pathways of tumour dissemination. In several human cancers, increased expression in primary tumours of a new member of the vascular endothelial growth factor (VEGF) family, namely VEGF-C, is correlated with regional lymph node metastasis. Experimental studies using transgenic mice overexpressing VEGF-C or xenotransplantation of VEGF-C-expressing tumour cells into immunodeficient mice have demonstrated a role for VEGF-C in tumour lymphangiogenesis and the subsequent formation of lymph node metastasis. However, there is at present very little evidence for lymphangiogenesis in human tumours, which is at variance with the data obtained in animal models. Nonetheless, the striking correlation between levels of VEGF-C in primary tumours and lymph node metastases exists. This suggests that VEGF-C may activate pre-existing lymphatics which then become actively involved in tumour cell chemotaxis, intralymphatic intravasation and distal dissemination. The role of VEGF-C in human tumour metastasis is therefore likely to involve lymphangiogenesis as well as its capacity to induce activation of pre-existing lymphatic endothelium.