Targeting tumor lymphangiogenesis: an update.

Various human tumors preferentially metastasize by lymphatic route and lymphovascular invasion predicts lymph node metastasis. In this review article, we will summarize recent literature data concerning lymphangiogenesis, focusing on tumor lymphangiogenesis. In detail, we try to answer some important questions related to: a) The specificity of lymphatic endothelial cell markers; b) The differential characteristics of lymphatic vessels in tumors; c) The interplay between different lymphangiogenic factors; d) The role of pre-existing and newly-formed lymphatic vessels in tumors and their proliferative potential; e) The role of lymphatic vessels in tumor metastases; e) The prognostic significance of lymphatic microvascular density in tumors; f) The inhibition of lymphangiogenesis in tumors.