Tumor Lymphangiogenesis as a Potential Therapeutic Target
Figure 1
Embryonic lymphangiogenesis versus tumor lymphangiogenesis. (a) During early lymphatic vessel development, lymphatic endothelial precursor cells (SOX18+/COUP-TFII+/PROX-1+) from the CV migrate outwards and form lymph sacs (LS), from which lymphatic vessels start to extend throughout the body. (b) In a tumor microenvironment, various lymphatic growth factors are secreted from tumor cells, inflammatory cells (e.g., TAMs), and stroma cells. These factors stimulate the formation of tumor neolymphatics, either in the peritumoral or intratumoral area, which facilitate the intravasation of cancer cells into lymphatic vessels. Interestingly, several key early factors in embryonic lymphangiogenesis also play critical roles during tumor lymphangiogenesis. In particular, SOX18 is not required for maintenance of adult lymphatics but appears to be reactivated and regulate the formation of tumor neolymphatics. CV, cardinal vein; LS, lymph sac; dpc, days coitum; GF, growth factor; LN, lymph node; DLN, draining lymph node; TAMs, tumor-associated macrophages.
