Development of lymphatic vessels: tumour lymphangiogenesis and lymphatic invasion.

In human solid cancer, the lymph node status is the most important prognostic indicator for the clinical outcome of patients. Follow-up data has shown that about 80% of metastasis follows an orderly pattern of progression via the lymphatic network while about 20% systemic metastasis occurs, bypassing the lymphatic system. Over the past few years, advances have been made in understanding the cellular and molecular aspects of physiological lymphangiogenesis and tumour-induced lymphangiogenesis, and the majority of studies point out to a positive correlation between tumour-induced lymphangiogenesis and lymphatic metastasis. However, the impact of intra- and peritumoural lymphatics on the tumour biology and the first steps of lymphatic metastasis, i.e. the invasion of tumour cells into the lymphatic vessels, are not well understood. We will give an outline of i. the physiological process of lymphangiogenesis, ii. tumour-induced lymphangiogenesis and lymphatic metastasis, iii. lymphatic invasion and the common pathways of tumour-lymphangiogenesis and lymphatic invasion. The growing interest in this topic has brought up a number of new molecular players in the field, which may provide the basis for a rational therapy against the process of lymphatic dissemination of tumour cells.