Lymphangiogenesis in tumors: What do we know?

Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. However, until recently consistent data regarding reliable lymphatic endothelial cell markers were lacking. Moreover, the presence of new formed lymphatic vessels was considered a largely disputable concept. Now, this scenario has changed significantly, owing to consistent reports describing novel lymphatic endothelial cell (LEC) markers, the demonstration of new formed lymphatic vessels within the bulk of the tumor in animal models and human neoplasms, and the characterization of the VEGF-C/VEGFR-3 pathway. We herein review the major breakthroughs in the field of lymphangiogenesis, with special emphasis on novel and reliable LEC markers, such as prox-1, LYVE-1, and podoplanin, as well as on the pathological assessment of lymphangiogenesis as a putative prognostic factor for human neoplasms.