Tumor Lymphanglogenesls: What We Know and Don't Know

摘要

The lymphatic vasculature represents a major conduit through which tumor cell metastasize. In addition to structural considerations and passive mechanisms that facilitate entry of tumor cells into lymphatic capillaries, a number of processes have been discovered whereby tumor cells actively promote their entry into the lymphatics. One of these processes is tumor-induced lymphangiogenesis. Activation of VEGFR-3 on lymphatic endothelial cells (LECs) by its ligands VEGF-C and/or VEGF-D produced by tumors is the best-studied regulator of tumor-induced lymphangiogenesis. However, a number of other pro-lymphangiogenic factors operative within tumors have additionally been discovered. Progress is being made in understanding the signal transduction pathways and their end points that orchestrate lymphangiogenesis. Together, these findings are supporting attempts to therapeutically interfere with tumor-induced lymphangiogenesis. Nevertheless, many outstanding issues remain to be addressed, including possible side effects of such therapeutic interference. Furthermore, additional active mechanisms that promote the formation of lymph node metastasis are emerging, including chemokine-mediated chemotaxis and remote tumor-induced changes in the lymph node microenvironment that support subsequent metastasis formation. The relative contribution of these different mechanisms to the process of metastasis remains to be investigated.