Lymphangiogenesis in malignant tumours: Does it occur?

The development of a vascular bed is essential for solid tumour growth and metastasis. In many tumours, mean vascular density can be related to the rate of metastasis and, therefore, to prognosis. In other tumour types, such as cutaneous melanoma and head-and-neck squamous cell carcinoma, this relation is absent. Until now, the reason for this has been unclear, but since these particular tumour types are also known for their propensity to spread via the lymphatic system, it may be speculated that the presence of a pre-existing lymphatic bed and the formation of new lymphatics (lymphangiogenesis) are important factors. Growth factors involved in lymphangiogenesis during embryogenesis have been recently identified and these are also expressed in many tumour types, but the existence of tumour-induced lymphangiogenesis has not so far been reported. Partly, this could be due to the lack of reliable endothelial markers, thereby hampering a consistent evaluation of lymphatic vasculature. This editorial discusses the role of the lymphatic bed in mediating the metastasis of solid tumours, summarizes known methods to detect lymphatics, and proposes a hypothetical mechanism of tumour-induced lymphangiogenesis.