Lymph node lymphangiogenesis: a new concept for modulating tumor metastasis and inflammatory process

The proliferation of lymphatic endothelial cells (LECs) occurs not only in tumor and inflamed tissues, but also in regional draining lymph nodes (LNs). The lymph node lymphangiogenesis (LNLG) has recently emerged as a prominent area in biomedical research, because it is involved in the pathogenesis of several human diseases. The LEC functional features and lymphatic remodeling regulated by lymphangiogenic factors actively promote tumor metastasis and the inflammation process. VEGF-A/VEGFR-2 and VEGF-C/-D/VEGFR-3 have been implicated as the prime mediators in inflammation- or tumor-induced LNLG. This knowledge may provide a foundation for further understanding of specific modification in the gene expression, cell migration, and differentiation of LECs and other cells in lymphatic-associated diseases. Importantly, it should be taken into consideration that inflammation and lymphangiogenesis are strongly linked in the formation and metastasis of cancer when designing therapeutic strategies.