WCCS/EADO 2016 | The role of lymphangiogenesis in melanoma

“Peter Petzelbauer, MD, of the Medical University of Vienna, Vienna, Austria, discusses the role of lymphangiogenesis in melanoma at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. He explains that normally, a tumor has to reach a certain size of several centimeters in order to home to other tissues to make metastasis. However, a melanoma tumor of a thickness of just 1mm is able to go to the central lymph node and cause systemic disease. It is very important to understand why these cells are so highly moveable and why these cells can so rapidly reach their central lymph node. Petzellbauer and his colleagues addressed this question by analyzing human derived melanoma cell lines and found that they have tremendous variance in expression of VEGF-C. VEGF-C is the key molecule that induces lymphangiogenesis and the amount of lymphangiogenesis strictly correlates with a chance of metastases. He explains that in order to understand why certain melanoma cells make a large amount of VEGF-Cs and others do not, patterns of RNA expression of these cells were screened. It was found that two MAP-Kinase pathways, the P38 and JNK pathway are responsible for the different behavior of these cells. If a melanoma cell has an active JNK pathway, this results in no VEGF-C production, a poor lymphangiogenic situation and a poor mobile situation. These cells however are highly proliferative. On the other hand, if you have an active P38 pathway, you get large amounts of VEGF-C expression and large amounts of lymphangiogenesis. These cells are not very proliferative but are highly mobile and can efficiently reach the central lymph nodes. Finally, he explains that when looking at human data, it has been found that expression patterns of these kinases in primary melanoma samples strictly correlates with metastases and survival.
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